ISTA Pharmaceuticals, Inc. (Nasdaq: ISTA), today announced highly statistically significant results from its initial analysis of the Company's U.S. Phase III clinical trials of Xibrom(TM) (bromfenac sodium ophthalmic solution) once-daily formulation. The multi-center studies evaluated Xibrom once-daily formulation versus placebo in over 500 patients who underwent cataract surgery. The preliminary results of the Xibrom Phase III trials demonstrated Xibrom was highly statistically significant in treating post-operative ocular pain and inflammation associated with cataract surgery. Based upon preliminary analyses, the safety profile is consistent with the currently marketed Xibrom formulation. The Xibrom once-daily formulation contains both a higher concentration of the active ingredient, bromfenac, and a new formulation compared to the original twice-daily product. If FDA-approved, this Xibrom formulation will provide patients with the most significant improvement to date in treating ocular pain and inflammation associated with cataract surgery, as it will be the only available once-a-day treatment.
Based upon the preliminary results of the studies and pending final analyses, ISTA plans to file a supplemental New Drug Application (sNDA) with the U.S. Food & Drug Administration in the second half of 2007 for the Xibrom once-daily formulation for the treatment of ocular pain and inflammation associated with cataract surgery.
"We believe these data represent the successful achievement of our efforts to improve upon Xibrom, our flagship product. The once-daily formulation will provide the most potent and conveniently dosed ophthalmic NSAID to patients undergoing cataract surgery. As studies show time and again, less-frequent dosing improves patient compliance, and we believe patients will benefit significantly should Xibrom once-daily receive FDA approval," stated Vicente Anido, Jr., Ph.D., ISTA's President and Chief Executive Officer. "We plan to complete our analysis of the Phase III data and announce detailed final results from these studies in a peer-reviewed forum."
Xibrom(TM) (bromfenac)
Xibrom is a topical non-steroidal anti-inflammatory compound for the treatment of ocular inflammation and pain. Xibrom, under a different trade name but identical formulation, was launched in Japan in 2000 by Senju Pharmaceuticals Co. Ltd. ISTA acquired U.S. marketing rights for Xibrom in May 2002 and launched the product in the U.S. in June 2005. Xibrom is the first and only FDA-approved twice-daily NSAID for inflammation and pain following cataract surgery, and in 2006, Xibrom became the second highest-prescribed topical NSAID by ophthalmologists on a dollar basis according to IMS data.
About ISTA
ISTA Pharmaceuticals is an ophthalmic pharmaceutical company. ISTA's products and product candidates addressing the $3.2 billion U.S. prescription ophthalmic industry include therapies for allergy, dry eye, vitreous hemorrhage, diabetic retinopathy, hyphema, glaucoma, ocular pain, and inflammation. The Company currently markets three products and is developing a strong product pipeline to fuel future growth and market share. The Company's product development and commercialization strategy is to launch a new product every 12 to 18 months, thereby continuing its growth to become the leading niche ophthalmic pharmaceutical company in the U.S. For additional information regarding ISTA, please visit ISTA Pharmaceuticals' website at http://www.istavision.com.
Any statements contained in this press release that refer to future events or other non-historical matters are forward-looking statements. Without limiting the foregoing, but by way of example, statements contained in this press release related to ISTA's plan to submit to the FDA an sNDA for the Xibrom once-daily formulation in the second half of 2007 and FDA's subsequent acceptance and approval of this sNDA, ISTA's plan to complete its analysis of the Xibrom once-daily Phase III data and announce in the future detailed final results in a peer-reviewed forum, the assumption that final results of the Xibrom once-daily Phase III data will be consistent with the preliminary results and support the filing of an sNDA, the potential benefits of Xibrom once-daily, if approved by FDA, for patients as compared to other currently marketed therapies, and ISTA's strategic objective to launch a new product every 12 to 18 months, thereby continuing its growth toward its goal of becoming the leading niche ophthalmic pharmaceutical company in the U.S., are forward-looking statements. Except as required by law, ISTA disclaims any intent or obligation to update any forward-looking statements. These forward- looking statements are based on ISTA's expectations as of the date of this press release and are subject to risks and uncertainties that could cause actual results to differ materially. Important factors that could cause actual results to differ from current expectations include, among others: the risk that full analysis of the Xibrom once-daily Phase III data will not reflect the preliminary Phase III results reported in this press release or be sufficient to support the submission of an sNDA; timely and successful implementation of ISTA's strategic initiatives; delays and uncertainties related to ISTA's research and development program (including the difficulty of predicting the timing or outcome of the Xibrom once-daily product development efforts and the FDA or other regulatory agency approval or actions); uncertainties and risks regarding market acceptance of and demand for ISTA's approved products (Xibrom once-daily if approved by FDA) and the impact of competitive products and pricing; uncertainties and risks related to the continued availability of third party sourced products and raw materials on commercially reasonable terms, or at all; uncertainties and risks related to successful compliance with FDA and or other governmental regulations applicable to ISTA's facilities, products and/or business; uncertainties and risks related to the scope, validity, and enforceability of patents related to ISTA's products and technologies and the impact of patents and other intellectual property rights held by third parties; and such other risks and uncertainties as detailed from time to time in ISTA's public filings with the U.S. Securities and Exchange Commission, including but not limited to ISTA's Annual Report on Form 10-K for the year ended December 31, 2005, and its Form 10Q for the quarters ended March 31, 2006, June 30, 2006, and September 30, 2006.
ISTA Pharmaceuticals, Inc.
http://www.istavision.com
March 5, 2007
Common Anesthetic May Induce Cell Death, Generation Of Alzheimer's-Associated Protein
A new study has found how one of the most commonly used anesthetics may produce Alzheimer's-like changes in the brain. Previous studies have shown that applying the anesthetic isoflurane to cultured neural cells can lead to generation of amyloid-beta protein -- the key component of senile plaques seen in the brains of Alzheimer's patients -- and to the cell-death process known as apoptosis. In the Feb. 7 Journal of Neuroscience, researchers from Massachusetts General Hospital (MGH) and colleagues describe how isoflurane may set off a process in which A-beta generation and apoptosis interact with and magnify each other. Since this work was done in cell cultures, it is unknown whether the findings reflect a possible effect of the anesthetic on human brains.
"Our studies have shown that isoflurane may induce a vicious cycle of apoptosis, amyloid-beta generation, and further rounds of apoptosis leading to cell death," says Zhongcong Xie, MD, PhD, of the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND), the study's lead author. "If future studies support these findings, they suggest that caution be used in choosing this anesthetic for elderly patients, who already are at increased risk for Alzheimer's and for postoperative cognitive dysfunction." Xie is also associated with the MGH Department of Anesthesia and Critical Care.
Alzheimer's disease is characterized by plaques within the brain of amyloid-beta protein (A-beta), which is toxic to brain cells. A-beta is formed when the larger amyloid precursor protein (APP) is clipped by two enzymes -- beta-secretase, also known as BACE, and gamma-secretase -- to release the A-beta fragment. Normal processing of APP by an enzyme called alpha-secretase produces an alternative, non-toxic protein.
Some studies have indicated that general anesthesia may increase the risk of developing Alzheimer's disease. It also is known that a small but significant number of surgical patients experience a form of dementia in the postoperative period, but there is insufficient evidence of a direct connection between anesthesia and the risk of dementia. Previous articles -- including a recent report from the same research team -- have shown that isoflurane increases both A-beta generation and apoptosis in several types of cultured cells. The current study was designed to investigate the relationship between isoflurane-induced apoptosis and A-beta generation.
In a series of experiments, the researchers first found that applying isoflurane to cultured neural cells increased the activation of the enzyme caspase -- a key player in a pathway leading to apoptosis -- with no change in A-beta generation or APP processing. When they applied isoflurane to neural cells that express APP and had been treated with a caspase inhibitor, the expected changes in APP processing and A-beta generation were significantly reduced, indicating that caspase activation is essential to the pathway leading to A-beta generation and aggregation.
The researchers also found that isoflurane appears to raise levels of the A-beta-releasing enzymes BACE and gamma secretase and that generation of A-beta plaques further increases isoflurane-induced caspase activation. In addition, adding A-beta to neuronal cells that do not express APP also increased caspase activation in response to isoflurane. Overall, the study's results define molecular pathways by which isoflurane induces deposition of A-beta, both directly and via caspase activation, and by which A-beta deposits lead to further caspase activation and apoptosis.
"Even though our findings and those from other studies suggest that isoflurane may affect Alzheimer's pathogenesis, these experiments were performed in cultured cells only," says Rudolph Tanzi, PhD, director of the MGH-MIND Genetics and Aging Research Unit and senior author of the current paper. "We need to conduct in vivo studies before we can determine whether these results might be relevant to the development of delirium or Alzheimer's disease in human patients." Tanzi is a professor of Neurology at Harvard Medical School, where Xie is an assistant professor of Anesthesia. The researchers also plan to investigate whether other anesthetic agents may produce the same results seen with isoflurane, which is the only anesthetic tested in previous studies.
###
Co-authors of the Journal of Neuroscience report are Yuanlin Dong and Uta Maeda, of MGH-MIND and MGH Anesthesia; Robert D. Moir, PhD, of MGH-MIND; and Weiming Xia, Deborah Culley, MD, and Gregory Crosby, MD, of Brigham and Women's Hospital. The study was supported by grants from the National Institutes of Health and the American Geriatrics Society.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, transplantation biology and photomedicine. MGH and Brigham and Women's Hospital are founding members of Partners HealthCare System, a Boston-based integrated health care delivery system.
Contact: Sue McGreevey
Massachusetts General Hospital
"Our studies have shown that isoflurane may induce a vicious cycle of apoptosis, amyloid-beta generation, and further rounds of apoptosis leading to cell death," says Zhongcong Xie, MD, PhD, of the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND), the study's lead author. "If future studies support these findings, they suggest that caution be used in choosing this anesthetic for elderly patients, who already are at increased risk for Alzheimer's and for postoperative cognitive dysfunction." Xie is also associated with the MGH Department of Anesthesia and Critical Care.
Alzheimer's disease is characterized by plaques within the brain of amyloid-beta protein (A-beta), which is toxic to brain cells. A-beta is formed when the larger amyloid precursor protein (APP) is clipped by two enzymes -- beta-secretase, also known as BACE, and gamma-secretase -- to release the A-beta fragment. Normal processing of APP by an enzyme called alpha-secretase produces an alternative, non-toxic protein.
Some studies have indicated that general anesthesia may increase the risk of developing Alzheimer's disease. It also is known that a small but significant number of surgical patients experience a form of dementia in the postoperative period, but there is insufficient evidence of a direct connection between anesthesia and the risk of dementia. Previous articles -- including a recent report from the same research team -- have shown that isoflurane increases both A-beta generation and apoptosis in several types of cultured cells. The current study was designed to investigate the relationship between isoflurane-induced apoptosis and A-beta generation.
In a series of experiments, the researchers first found that applying isoflurane to cultured neural cells increased the activation of the enzyme caspase -- a key player in a pathway leading to apoptosis -- with no change in A-beta generation or APP processing. When they applied isoflurane to neural cells that express APP and had been treated with a caspase inhibitor, the expected changes in APP processing and A-beta generation were significantly reduced, indicating that caspase activation is essential to the pathway leading to A-beta generation and aggregation.
The researchers also found that isoflurane appears to raise levels of the A-beta-releasing enzymes BACE and gamma secretase and that generation of A-beta plaques further increases isoflurane-induced caspase activation. In addition, adding A-beta to neuronal cells that do not express APP also increased caspase activation in response to isoflurane. Overall, the study's results define molecular pathways by which isoflurane induces deposition of A-beta, both directly and via caspase activation, and by which A-beta deposits lead to further caspase activation and apoptosis.
"Even though our findings and those from other studies suggest that isoflurane may affect Alzheimer's pathogenesis, these experiments were performed in cultured cells only," says Rudolph Tanzi, PhD, director of the MGH-MIND Genetics and Aging Research Unit and senior author of the current paper. "We need to conduct in vivo studies before we can determine whether these results might be relevant to the development of delirium or Alzheimer's disease in human patients." Tanzi is a professor of Neurology at Harvard Medical School, where Xie is an assistant professor of Anesthesia. The researchers also plan to investigate whether other anesthetic agents may produce the same results seen with isoflurane, which is the only anesthetic tested in previous studies.
###
Co-authors of the Journal of Neuroscience report are Yuanlin Dong and Uta Maeda, of MGH-MIND and MGH Anesthesia; Robert D. Moir, PhD, of MGH-MIND; and Weiming Xia, Deborah Culley, MD, and Gregory Crosby, MD, of Brigham and Women's Hospital. The study was supported by grants from the National Institutes of Health and the American Geriatrics Society.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, transplantation biology and photomedicine. MGH and Brigham and Women's Hospital are founding members of Partners HealthCare System, a Boston-based integrated health care delivery system.
Contact: Sue McGreevey
Massachusetts General Hospital
Scientific Research Highlights Of The American Academy Of Pain Medicine Annual Meeting
Pain medicine investigators presented preliminary research findings at poster sessions held during the 23rd annual meeting of the American Academy of Pain Medicine at the Hilton New Orleans Riverside Hotel/Morial Convention Center, February 7-10, 2007. The highlights are as follows:
* Internet not Primary Source for Illegally Obtained Prescription Analgesics By Addicts Seeking Methadone Treatment
Despite media reports suggesting that the Internet is the primary source for illegally obtained prescription opioids, only a small percentage of opioid analgesic addicts who are seeking methadone maintenance treatment reported this as a direct source of their drug supply.
Illegally obtained opioid medications present an ongoing and challenging dilemma to society at large, while also impacting the legitimate prescribing of opioids for those individuals with moderate to severe chronic pain conditions. The researchers analyzed questionnaires filled out by 3,294 persons seeking treatment for addiction at 73 methadone treatment programs who indicated that a prescription opioid analgesic was the primary drug they abused to learn how opioid analgesic abusers reportedly obtained their drug. The most commonly reported sources for obtaining opioid analgesics included: dealers (79.96%), friends or relatives (51.3%), physician prescription (30.17%), emergency room visits (13.53%), theft (6.48%), forged prescription (2.48%), Internet (2.9%), and other (not specified) (2.7%).
Investigators: Ann T. Kline, MS, Purdue Pharma L.P., Stamford, CT; Meredith Y. Smith, MPA, PhD, Purdue Pharma L.P., Stamford, CT; J. David Haddox, DDS, MD, Purdue Pharma L.P., Stamford, CT; John P. Fitzgerald, MS, LPC, CAS, Purdue Pharma L.P., Stamford, CT; Andrew Rosenblum, PhD, National Development and Research Institutes (NDRI), New York, NY; Chunki Fong, MS, NDRI, New York, NY; Mark Parrino, MPA, American Association for the Treatment of Opioid Dependence (AATOD), New York, NY; and Carleen Maxwell, MPH, AATOD, New York, NY.
* Report Characterizes Opioid Analgesic Abuse
Opioid analgesic abuse is more prevalent in rural areas and is growing in popularity among teenagers.
Although numerous US surveillance systems currently report on opioid analgesic abuse, there is a need for additional descriptive and interpretive data, not only to confirm and characterize the cases, but to guide targeted intervention efforts. The researchers conducted 258 telephone interviews in 40 states with a wide range of contacts, including law enforcement officers, physicians, pharmacists, and drug abuse treatment staff. The reports from the local sources indicated that hydrocodone and oxycodone (immediate-release and extended-release) were reported to be the most frequently abused and diverted opioid analgesics; opioid analgesic abuse is not confined to rural areas; opioid analgesic abuse appears to be rising among teenagers; and abusers often perceive prescription drugs to be safer to use than illicit drugs.
Other key findings include the abuse of antidepressants to reduce the side effects of methamphetamine; abuse of prescription drugs rising in Mormon communities and on Native American reservations; and local government officials are being forced to redirect resources from diversion and abuse of prescription drugs to combat a rising methamphetamine problem. Interpretation of quantitative reports of opioid analgesic abuse and diversion are substantially enriched by the addition of detailed, descriptive field-based inquiries.
Investigators: John P. Fitzgerald, MS, LPC, CAS, Meredith Y. Smith, Ann T. Kline, and J. David Haddox, DDS, MD, Purdue Pharma L.P., Stamford, CT.
* Spinal Cord Stimulation Can Relieve Low Back Pain
Careful patient selection and stimulation programming can improve management of axial low back pain with spinal cord stimulation. The researchers note that axial low back pain is a novel indication for spinal cord stimulation. Technological capabilities of the spinal cord stimulation system, particularly fractionalized current across contacts, uniquely provide the type of stimulation needed to relieve axial back pain.
Spinal cord stimulation effectively manages a range of painful etiologies, but little published evidence supports its use for axial low back pain. The researchers studied 226 spinal cord stimulators (Precision™, Advanced Bionics) implanted in patients with axial low back pain to assess the therapeutic value of spinal cord stimulation in treating axial back pain associated with failed back surgery syndrome. Pain scores, quality of life, and disability assessments were gathered at three, six, and 12 months after activation of the spinal cord stimulation system and compared to baseline measures. Additional assessments were made at 3.5 months after a two-week period of no stimulation. The investigators found that spinal cord stimulation significantly reduced axial low back pain, and when present, leg and foot pain, from baseline at all time points. With stimulation off, pain scores returned to near baseline. Quality of life and disability also significantly improved with spinal cord stimulation. Of 226 temporary trials, 172 (76%) were successful, and 159 subjects (70%) received permanent implants. Reported here are outcome data for all subjects through 3.5 months, and for those subjects who have completed six- and 12-month evaluations. A subsequent report will include all 12-month data. This study represents the largest prospective experience reported to date for spinal cord stimulation in axial low back pain.
Investigators: Benchmark Clinical Study Working Group, Advanced Bionics, Valencia, CA; Jim Thacker, MS, Enteromedics, St. Paul, MN; Todd Gross, PhD, Advanced Bionics, Valencia, CA; and Allison Foster, PhD, Advanced Bionics, Valencia, CA.
* More Patient Education Necessary to Manage Sickle Cell Pain
A significant number of people with sickle cell disease reported significant pain and currently use a combination of pharmacological and non-pharmacological methods to manage pain events.
A number of sickle cell patients manage a great deal of their pain episodes at home. The researchers studied 46 questionnaires completed by sickle cell patients to determine if provision of increased knowledge and skills in the use of pharmacologic and non-pharmacologic methods will provide sickle cell patients with greater self-management of pain, improved quality of life and decreased hospitalizations. The investigators found that the average age of respondents was 30 years and the majority were females (58.4%). 57.9% have a diagnosis of sickle cell anemia (hemoglobin SS), while 38.6% had hemoglobin SC disease, and 5% have other hemoglobinopathies. About 22.2% of the respondents were taking opioids analgesics for pain control. About 44% reported experiencing mild-moderate pain events within the last six months. 60.0% had experienced moderate-severe pain requiring a visit to a medical facility within the past six months. More than 75% reported pain greater than 5 on a 0 - 10 point scale when asked to rate their pain during these events.
Relaxation was reported as being used by 77.8% of respondents to help control pain, heating pad was used by 3.7%, and 14.8% report using other techniques to help manage pain events. The researchers conclude that there are opportunities for education and other interventions to improve such techniques and empower patients to achieve improved pain control. As a corollary, this will decrease health care utilization and improve patients' well being and family life for this group of patients.
Investigators: Arleen Anderson, Wendy Thompson, Stephen Tafor, and Ike Eriator, from the University of Mississippi, Jackson, MS.
* Novel Radiofrequency Treatment Shows Promise for Lumbar Pain
Intradiscal biacuplasty is an effective procedure to treat chronic discogenic pain. Improvement in pain scores and functional capacity can be observed much earlier with intradiscal biacuplasty than with intradiscal electrothermal therapy suggesting some additional or/and different mechanisms of action. It also appears to be more effective than intradiscal electrothermal therapy producing more than 50% of the pain relief in more than 50% of patients.
Intradiscal electrothermal therapy has produced variable results in the pain reduction and functional improvement in patients with axial discogenic pain. A new procedure called intradiscal biacuplasty utilizes two radiofrequency electrodes placed on the opposite posterolateral sides of the treated annulus. This procedure is minimally invasive and provides an alternative to lumbar fusion or disc replacement surgery. The researchers completed a pilot study of 13 patients who received intradiscal biacuplasty and were followed for six months. Following provocative discography patients underwent intradiscal biacuplasty. There were significant improvements of all of the indices (SF-36, Oswestry, Visual Analog Scale pain scores and opioid use) at the first follow-up at one month. Those improvements were maintained throughout six months of follow-up. At six months after intradiscal biacuplasty, patient's median pain scores measured by Visual Analog Scale decreased from 7 to 3. Functional capacity significantly improved with Oswestry scores median decrease from 25 to 18, and SF-36 PF median increase from 55 to 70. Median SF-36 BP score increased from 35 to 58. Median opioid use expressed in morphine sulphate mg equivalents decreased from 40 to 5 mg. There were no significant differences in any of the indices from first to sixth month after intradiscal biacuplasty. There were eight of 13 patients who had Visual Analog Scale pain scores decreased by three or more points. There were no complications perioperatively or during follow-up.
Investigators: Leonardo Kapural, MD, PhD, Alan Ng, MD, and Nagy Mekhail, MD, PhD., from Cleveland Clinic Foundation, Cleveland, OH.
###
Founded in 1983, AAPM is a medical specialty society representing physicians practicing in the field of pain medicine. Information is available on the practice of pain medicine at http://www.painmed.org/.
Contact: Amy Jenkins
American Academy of Pain Medicine
* Internet not Primary Source for Illegally Obtained Prescription Analgesics By Addicts Seeking Methadone Treatment
Despite media reports suggesting that the Internet is the primary source for illegally obtained prescription opioids, only a small percentage of opioid analgesic addicts who are seeking methadone maintenance treatment reported this as a direct source of their drug supply.
Illegally obtained opioid medications present an ongoing and challenging dilemma to society at large, while also impacting the legitimate prescribing of opioids for those individuals with moderate to severe chronic pain conditions. The researchers analyzed questionnaires filled out by 3,294 persons seeking treatment for addiction at 73 methadone treatment programs who indicated that a prescription opioid analgesic was the primary drug they abused to learn how opioid analgesic abusers reportedly obtained their drug. The most commonly reported sources for obtaining opioid analgesics included: dealers (79.96%), friends or relatives (51.3%), physician prescription (30.17%), emergency room visits (13.53%), theft (6.48%), forged prescription (2.48%), Internet (2.9%), and other (not specified) (2.7%).
Investigators: Ann T. Kline, MS, Purdue Pharma L.P., Stamford, CT; Meredith Y. Smith, MPA, PhD, Purdue Pharma L.P., Stamford, CT; J. David Haddox, DDS, MD, Purdue Pharma L.P., Stamford, CT; John P. Fitzgerald, MS, LPC, CAS, Purdue Pharma L.P., Stamford, CT; Andrew Rosenblum, PhD, National Development and Research Institutes (NDRI), New York, NY; Chunki Fong, MS, NDRI, New York, NY; Mark Parrino, MPA, American Association for the Treatment of Opioid Dependence (AATOD), New York, NY; and Carleen Maxwell, MPH, AATOD, New York, NY.
* Report Characterizes Opioid Analgesic Abuse
Opioid analgesic abuse is more prevalent in rural areas and is growing in popularity among teenagers.
Although numerous US surveillance systems currently report on opioid analgesic abuse, there is a need for additional descriptive and interpretive data, not only to confirm and characterize the cases, but to guide targeted intervention efforts. The researchers conducted 258 telephone interviews in 40 states with a wide range of contacts, including law enforcement officers, physicians, pharmacists, and drug abuse treatment staff. The reports from the local sources indicated that hydrocodone and oxycodone (immediate-release and extended-release) were reported to be the most frequently abused and diverted opioid analgesics; opioid analgesic abuse is not confined to rural areas; opioid analgesic abuse appears to be rising among teenagers; and abusers often perceive prescription drugs to be safer to use than illicit drugs.
Other key findings include the abuse of antidepressants to reduce the side effects of methamphetamine; abuse of prescription drugs rising in Mormon communities and on Native American reservations; and local government officials are being forced to redirect resources from diversion and abuse of prescription drugs to combat a rising methamphetamine problem. Interpretation of quantitative reports of opioid analgesic abuse and diversion are substantially enriched by the addition of detailed, descriptive field-based inquiries.
Investigators: John P. Fitzgerald, MS, LPC, CAS, Meredith Y. Smith, Ann T. Kline, and J. David Haddox, DDS, MD, Purdue Pharma L.P., Stamford, CT.
* Spinal Cord Stimulation Can Relieve Low Back Pain
Careful patient selection and stimulation programming can improve management of axial low back pain with spinal cord stimulation. The researchers note that axial low back pain is a novel indication for spinal cord stimulation. Technological capabilities of the spinal cord stimulation system, particularly fractionalized current across contacts, uniquely provide the type of stimulation needed to relieve axial back pain.
Spinal cord stimulation effectively manages a range of painful etiologies, but little published evidence supports its use for axial low back pain. The researchers studied 226 spinal cord stimulators (Precision™, Advanced Bionics) implanted in patients with axial low back pain to assess the therapeutic value of spinal cord stimulation in treating axial back pain associated with failed back surgery syndrome. Pain scores, quality of life, and disability assessments were gathered at three, six, and 12 months after activation of the spinal cord stimulation system and compared to baseline measures. Additional assessments were made at 3.5 months after a two-week period of no stimulation. The investigators found that spinal cord stimulation significantly reduced axial low back pain, and when present, leg and foot pain, from baseline at all time points. With stimulation off, pain scores returned to near baseline. Quality of life and disability also significantly improved with spinal cord stimulation. Of 226 temporary trials, 172 (76%) were successful, and 159 subjects (70%) received permanent implants. Reported here are outcome data for all subjects through 3.5 months, and for those subjects who have completed six- and 12-month evaluations. A subsequent report will include all 12-month data. This study represents the largest prospective experience reported to date for spinal cord stimulation in axial low back pain.
Investigators: Benchmark Clinical Study Working Group, Advanced Bionics, Valencia, CA; Jim Thacker, MS, Enteromedics, St. Paul, MN; Todd Gross, PhD, Advanced Bionics, Valencia, CA; and Allison Foster, PhD, Advanced Bionics, Valencia, CA.
* More Patient Education Necessary to Manage Sickle Cell Pain
A significant number of people with sickle cell disease reported significant pain and currently use a combination of pharmacological and non-pharmacological methods to manage pain events.
A number of sickle cell patients manage a great deal of their pain episodes at home. The researchers studied 46 questionnaires completed by sickle cell patients to determine if provision of increased knowledge and skills in the use of pharmacologic and non-pharmacologic methods will provide sickle cell patients with greater self-management of pain, improved quality of life and decreased hospitalizations. The investigators found that the average age of respondents was 30 years and the majority were females (58.4%). 57.9% have a diagnosis of sickle cell anemia (hemoglobin SS), while 38.6% had hemoglobin SC disease, and 5% have other hemoglobinopathies. About 22.2% of the respondents were taking opioids analgesics for pain control. About 44% reported experiencing mild-moderate pain events within the last six months. 60.0% had experienced moderate-severe pain requiring a visit to a medical facility within the past six months. More than 75% reported pain greater than 5 on a 0 - 10 point scale when asked to rate their pain during these events.
Relaxation was reported as being used by 77.8% of respondents to help control pain, heating pad was used by 3.7%, and 14.8% report using other techniques to help manage pain events. The researchers conclude that there are opportunities for education and other interventions to improve such techniques and empower patients to achieve improved pain control. As a corollary, this will decrease health care utilization and improve patients' well being and family life for this group of patients.
Investigators: Arleen Anderson, Wendy Thompson, Stephen Tafor, and Ike Eriator, from the University of Mississippi, Jackson, MS.
* Novel Radiofrequency Treatment Shows Promise for Lumbar Pain
Intradiscal biacuplasty is an effective procedure to treat chronic discogenic pain. Improvement in pain scores and functional capacity can be observed much earlier with intradiscal biacuplasty than with intradiscal electrothermal therapy suggesting some additional or/and different mechanisms of action. It also appears to be more effective than intradiscal electrothermal therapy producing more than 50% of the pain relief in more than 50% of patients.
Intradiscal electrothermal therapy has produced variable results in the pain reduction and functional improvement in patients with axial discogenic pain. A new procedure called intradiscal biacuplasty utilizes two radiofrequency electrodes placed on the opposite posterolateral sides of the treated annulus. This procedure is minimally invasive and provides an alternative to lumbar fusion or disc replacement surgery. The researchers completed a pilot study of 13 patients who received intradiscal biacuplasty and were followed for six months. Following provocative discography patients underwent intradiscal biacuplasty. There were significant improvements of all of the indices (SF-36, Oswestry, Visual Analog Scale pain scores and opioid use) at the first follow-up at one month. Those improvements were maintained throughout six months of follow-up. At six months after intradiscal biacuplasty, patient's median pain scores measured by Visual Analog Scale decreased from 7 to 3. Functional capacity significantly improved with Oswestry scores median decrease from 25 to 18, and SF-36 PF median increase from 55 to 70. Median SF-36 BP score increased from 35 to 58. Median opioid use expressed in morphine sulphate mg equivalents decreased from 40 to 5 mg. There were no significant differences in any of the indices from first to sixth month after intradiscal biacuplasty. There were eight of 13 patients who had Visual Analog Scale pain scores decreased by three or more points. There were no complications perioperatively or during follow-up.
Investigators: Leonardo Kapural, MD, PhD, Alan Ng, MD, and Nagy Mekhail, MD, PhD., from Cleveland Clinic Foundation, Cleveland, OH.
###
Founded in 1983, AAPM is a medical specialty society representing physicians practicing in the field of pain medicine. Information is available on the practice of pain medicine at http://www.painmed.org/.
Contact: Amy Jenkins
American Academy of Pain Medicine
March 4, 2007
Labopharm To Present Data At The 23rd Annual American Academy Of Pain Medicine Meeting
Labopharm Inc. (TSX: DDS; NASDAQ: DDSS) today announced that it will present two posters at the 23rd Annual American Academy of Pain Medicine (AAPM) Meeting to be held February 7 to 10, 2007 in New Orleans. The first poster presents efficacy and safety data from the Company's U.S. Phase III clinical trial (study MDT3-005) for its once-daily formulation of tramadol ("Tramadol Contramid(R) OAD") and the second presents data on the bioavailability of Tramadol Contramid(R) OAD compared with that of immediate-release (IR) Ultram(R) tablets.
Tramadol Contramid(R) OAD: A Placebo-Controlled Study Demonstrates
Efficacy and Safety in the Management of Pain
The positive Phase III study comparing Tramadol Contramid(R) OAD to placebo in patients diagnosed with moderate to severe pain associated with osteoarthritis of the knee (study MDT3-005) achieved its primary endpoint, demonstrating a statistically significantly greater average reduction in the Pain Intensity Numerical Rating Scale (PI-NRS) score compared to placebo (p=0.0157) using the last observation carried forward (LOCF) statistical method. Other results from the trial are as follows:
- The mean improvement on the PI-NRS throughout the study was significantly greater for Tramadol Contramid(R) OAD compared to placebo (p< 0.0001) based on the Time Weighted Analysis.
- The responder analysis showed that there was a statistically significantly greater percentage of responders in the Tramadol Contramid(R) OAD treatment group compared to the placebo group, irrespective of the response level (p= 0.035 for an improvement of at least 2 points). In addition, patients randomized to Tramadol Contramid(R) OAD achieved improvement significantly sooner than patients randomized to placebo; a 3 point improvement in the PI-NRS score was achieved in 16 days in the Tramadol Contramid(R) OAD group as compared to the placebo group, which required 39 days before achieving similar improvement (p< 0.0001).
- The Patient and Physician Global Impressions of Change indicate a high level of satisfaction with the analgesic effect among both patients and their physicians. At the end of the study, 80% of patients in the Tramadol Contramid(R) OAD group indicated that their condition had improved as compared to 69% of patients in the placebo group (p= 0.0002). Similar results were observed on the Physician Global Impression of Change (p= 0.0042).
- The relatively low incidence of the most common adverse events reported during the double-blind phase and their generally low intensity support the safety of Tramadol Contramid(R) OAD.
These results support the use of Tramadol Contramid(R) OAD given once daily as an efficacious and safe treatment for the management of pain.
Comparative Bioavailability of Tramadol Contramid(R) OAD and Tramadol Immediate-Release Tablets (Ultram(R)
In two separate (single-dose and multiple-dose) open-label, randomized, two-way crossover studies, the bioavailability of Tramadol Contramid(R) OAD 200 mg tablets was compared to immediate-release (IR) Ultram(R) 50 mg tablets following single-dose and multiple-dose (at steady state) administration. The conclusions of the trial are as follows:
- Following single-dose administration, the initial absorption of tramadol from Tramadol Contramid(R) OAD 200 mg is rapid and comparable to that of Ultram(R) 50 mg;
- Effective plasma concentrations are attained within one hour of dosing and maintained for a full 24-hour post-dose period following single-dose administration of Tramadol Contramid(R) OAD 200 mg.
- Steady state is attained within 48 hours following initiation of dosing with Tramadol Contramid(R) OAD 200 mg, allowing for titration up to the higher doses on the third day;
- Tramadol Contramid(R) OAD 200 mg tablets provide equivalent exposure to the active ingredient compared with Ultram(R) 50 mg tablets following both single- and multiple-dose administration.
The posters will be available on Labopharm's web site (http://www.labopharm.com) on Sunday, February 11, 2007.
About the American Academy of Pain Medicine and Annual Meeting
The American Academy of Pain Medicine (AAPM) is the medical specialty society representing physicians practicing in the field of Pain Medicine. As a medical specialty society, the Academy is involved in education, training, advocacy, and research in the specialty of Pain Medicine. The Academy's Annual Meeting will feature a wide range of educational opportunities, new products and networking with Pain Medicine colleagues.
About Labopharm Inc.
Labopharm Inc. is an international specialty pharmaceutical company focused on the development of drugs incorporating the Company's proprietary advanced controlled-release technologies. The Company's lead product, a once-daily formulation of the analgesic tramadol, has been approved and launched in Europe and is currently under review for approval by the U.S. Food and Drug Administration. For more information, please visit http://www.labopharm.com.
This press release contains forward-looking statements, which reflect the Corporation's current expectations regarding future events. The forward-looking statements involve risks and uncertainties. Actual events could differ materially from those projected herein and depend on a number of factors, including the uncertainties related to the regulatory process and the commercialization of the Corporation's products thereafter, if they are approved. Investors should consult the Corporation's ongoing quarterly filings and annual reports for additional information on risks and uncertainties relating to these forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. The Corporation disclaims any obligation to update these forward-looking statements.
Labopharm Inc.
http://www.labopharm.com
Tramadol Contramid(R) OAD: A Placebo-Controlled Study Demonstrates
Efficacy and Safety in the Management of Pain
The positive Phase III study comparing Tramadol Contramid(R) OAD to placebo in patients diagnosed with moderate to severe pain associated with osteoarthritis of the knee (study MDT3-005) achieved its primary endpoint, demonstrating a statistically significantly greater average reduction in the Pain Intensity Numerical Rating Scale (PI-NRS) score compared to placebo (p=0.0157) using the last observation carried forward (LOCF) statistical method. Other results from the trial are as follows:
- The mean improvement on the PI-NRS throughout the study was significantly greater for Tramadol Contramid(R) OAD compared to placebo (p< 0.0001) based on the Time Weighted Analysis.
- The responder analysis showed that there was a statistically significantly greater percentage of responders in the Tramadol Contramid(R) OAD treatment group compared to the placebo group, irrespective of the response level (p= 0.035 for an improvement of at least 2 points). In addition, patients randomized to Tramadol Contramid(R) OAD achieved improvement significantly sooner than patients randomized to placebo; a 3 point improvement in the PI-NRS score was achieved in 16 days in the Tramadol Contramid(R) OAD group as compared to the placebo group, which required 39 days before achieving similar improvement (p< 0.0001).
- The Patient and Physician Global Impressions of Change indicate a high level of satisfaction with the analgesic effect among both patients and their physicians. At the end of the study, 80% of patients in the Tramadol Contramid(R) OAD group indicated that their condition had improved as compared to 69% of patients in the placebo group (p= 0.0002). Similar results were observed on the Physician Global Impression of Change (p= 0.0042).
- The relatively low incidence of the most common adverse events reported during the double-blind phase and their generally low intensity support the safety of Tramadol Contramid(R) OAD.
These results support the use of Tramadol Contramid(R) OAD given once daily as an efficacious and safe treatment for the management of pain.
Comparative Bioavailability of Tramadol Contramid(R) OAD and Tramadol Immediate-Release Tablets (Ultram(R)
In two separate (single-dose and multiple-dose) open-label, randomized, two-way crossover studies, the bioavailability of Tramadol Contramid(R) OAD 200 mg tablets was compared to immediate-release (IR) Ultram(R) 50 mg tablets following single-dose and multiple-dose (at steady state) administration. The conclusions of the trial are as follows:
- Following single-dose administration, the initial absorption of tramadol from Tramadol Contramid(R) OAD 200 mg is rapid and comparable to that of Ultram(R) 50 mg;
- Effective plasma concentrations are attained within one hour of dosing and maintained for a full 24-hour post-dose period following single-dose administration of Tramadol Contramid(R) OAD 200 mg.
- Steady state is attained within 48 hours following initiation of dosing with Tramadol Contramid(R) OAD 200 mg, allowing for titration up to the higher doses on the third day;
- Tramadol Contramid(R) OAD 200 mg tablets provide equivalent exposure to the active ingredient compared with Ultram(R) 50 mg tablets following both single- and multiple-dose administration.
The posters will be available on Labopharm's web site (http://www.labopharm.com) on Sunday, February 11, 2007.
About the American Academy of Pain Medicine and Annual Meeting
The American Academy of Pain Medicine (AAPM) is the medical specialty society representing physicians practicing in the field of Pain Medicine. As a medical specialty society, the Academy is involved in education, training, advocacy, and research in the specialty of Pain Medicine. The Academy's Annual Meeting will feature a wide range of educational opportunities, new products and networking with Pain Medicine colleagues.
About Labopharm Inc.
Labopharm Inc. is an international specialty pharmaceutical company focused on the development of drugs incorporating the Company's proprietary advanced controlled-release technologies. The Company's lead product, a once-daily formulation of the analgesic tramadol, has been approved and launched in Europe and is currently under review for approval by the U.S. Food and Drug Administration. For more information, please visit http://www.labopharm.com.
This press release contains forward-looking statements, which reflect the Corporation's current expectations regarding future events. The forward-looking statements involve risks and uncertainties. Actual events could differ materially from those projected herein and depend on a number of factors, including the uncertainties related to the regulatory process and the commercialization of the Corporation's products thereafter, if they are approved. Investors should consult the Corporation's ongoing quarterly filings and annual reports for additional information on risks and uncertainties relating to these forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. The Corporation disclaims any obligation to update these forward-looking statements.
Labopharm Inc.
http://www.labopharm.com
Anesiva Presents Data On Pain Drug, 4975, Demonstrating Pain Reduction For Up To Two Weeks After Knee Replacement Surgeries
Anesiva, Inc. (Nasdaq: ANSV) presented positive, clinical data from a Phase 2 clinical trial in total knee replacement surgeries with drug candidate, 4975, the company's novel, long-acting, non-opioid drug candidate being developed for site-specific, moderate-to-severe pain. As was previously reported when top- line data were released, 4975 demonstrated pain reduction at all pre-specified time intervals in the study. Data presented yesterday showed a trend toward lower concomitant morphine usage in the 4975-treated group over the placebo group, one of multiple secondary endpoints. The study also met its primary objective of safety and tolerability. These data were presented by clinical investigators at the American Academy of Pain Medicine Meeting in New Orleans, Louisiana.
"A key attribute of 4975 is its potential to significantly reduce pain and provide additional benefit to patients receiving multimodal analgesia. We were pleased to see that the patients in the knee replacement study who were treated with 4975 showed a trend toward reduced morphine usage to manage their pain," said Daniel J. Gennevois, M.D., senior vice president of clinical development at Anesiva. "Following our successful meeting with the FDA, we now have a clear development pathway for 4975 and are focusing our near-term efforts in two areas-post-surgical pain and pain associated with osteoarthritis-both areas in which 4975 has shown its ability to reduce pain following just a single administration."
All patients in the trial received progressive multimodal analgesia, and despite the multiple medications that patients receive following knee replacement surgeries, they still experience moderate to severe pain. Additionally, post-operatively, all patients in the trial self-administered intravenous morphine via patient controlled analgesia (PCA) pump to achieve satisfactory analgesia for approximately 48-hours following surgery, and a trend toward lower morphine usage was demonstrated in the 4975-treated group versus the placebo-treated group. This is an important finding, as an advantage of 4975 is its potential to reduce the need for opioid drugs, which are well known to have side effects such as sedation, respiratory depression, euphoria, and nausea and vomiting during acute use, and constipation and physical dependence during chronic use. In clinical studies to date, 4975 has not had the side effects often associated with other conventional pain medications and has been shown to be well tolerated. The incidence of treatment-related adverse events (AEs) was generally comparable between the groups with the most frequently reported AEs being localized or peripheral redness and swelling. Most AEs were mild in severity and no patient in the 4975 group withdrew from the study because of an AE.
As was previously reported, the difference in average daily pain scores upon ambulation between the 4975-treated group (n=25) and the placebo group (n=25) on day one was statistically significant (p=0.0273) and showed a relative difference in pain of 24 percent. On a numerical rating scale of zero to 10, the average pain score for the treated group was 5.4 compared with the placebo group's average of 7.1. It is noteworthy that this difference was detected despite all patients being on concomitant morphine. On day 14, the patients' "worst pain in the previous 24-hour period" using the Brief Pain Inventory form showed a relative difference of 34 percent with the average pain scores being 3.9 and 5.9 for the treated group and placebo group, respectively (p=0.0071). This long-lasting analgesic effect may provide benefit to patients receiving a total knee replacement since they must endure an intensive and lengthy rehabilitation period in order to ensure successful function of the new knee. The analysis of additional exploratory efficacy endpoints favored the 4975 group over the placebo group including average daily pain scores at multiple time points: day 1, day 2, days 1-2, days 3-7, days 8-14, days 1-14 and days 3-14. In addition, the measurement of pain interference with activities favored the 4975 group over the placebo group at most of the time points measured.
The Phase 2 study involved 50 knee replacement surgery patients who were randomized to receive either a single dose of 4975 or placebo, which was dripped by syringe into the wound prior to closure. In addition to general anesthesia, concomitant analgesics included a preoperative femoral nerve block, intraoperative bupivacaine via wound infiltration and pre-, intra-, and post-operative intravenous ketorolac. Additionally, post-operatively, patients had the option to self administer intravenous morphine for approximately 48 hours post-surgery. After morphine was discontinued, patients could receive supplemental hydrocodone/acetaminophen as needed to manage their pain.
A follow-on Phase 2 clinical trial in approximately 50 patients undergoing knee replacement surgeries is expected to begin during the first half of 2007. The trial will evaluate a higher dose of 4975 than that used in the previous study. Anesiva plans to initiate a Phase 3 trial in knee replacement surgery patients in the second half of 2007.
Total knee replacement (also known as total knee arthroplasty) is performed in patients with end-stage osteoarthritis of the knee. These patients have disabling pain which imposes severe limitations on their mobility, and knee replacement is performed with the goal of restoring or improving patients' quality of life. There were an estimated 470,000 total knee replacement procedures performed in the United States in 2005, and the number of replacements will continue to grow as the average age of the U.S. population increases and as these individuals conduct more active lives. The American Academy of Orthopedic Surgeons projects that approximately 3.5 million of these procedures will be done each year by 2030.
How 4975 May Address Need for Long-Duration, Well-Tolerated Pain Relief
4975 is long-acting, with the potential to provide pain relief for weeks or months after just a single localized treatment. It is a non-opioid TRPV1 agonist with a unique mechanism of action that provides a long-lasting, localized effect on C-fibers and blocks the transmission of aching, throbbing pain caused by major surgical procedures and end-stage osteoarthritis. Because it selectively acts on pain-sensing nerve endings, 4975 does not affect other nerve fibers necessary for sensory or motor sensations, such as those needed to sense temperature or pressure.
About Anesiva
Anesiva, Inc. is a late-stage biopharmaceutical company that seeks to be the leader in the development and commercialization of novel therapeutic treatments for pain. The company has two drug candidates in development for multiple pain-related indications. A New Drug Application (NDA) has been filed for the most advanced product, Zingo(TM). The second product in the pipeline, 4975, has been shown to reduce pain after only a single administration for weeks to months in multiple settings in numerous mid-stage clinical trials for site-specific, moderate-to-severe pain. Anesiva is based in South San Francisco, CA. For more information about Anesiva's leadership in the development of products for pain management, and an overview of the clinical challenges being addressed by its product candidates, go to http://www.anesiva.com.
Forward-Looking Statements
This press release includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Words such as "expect," "estimate," "project," "budget," "forecast," "anticipate," "intend," "plan," "may," "will," "could," "should," "believes," "predicts," "potential," "continue," and similar expressions are intended to identify such forward-looking statements. Forward- looking statements in this press release include matters that involve known and unknown risks, uncertainties and other factors that may cause actual results, levels of activity, performance or achievements to differ materially from results expressed or implied by this press release. Such risk factors include, among others, whether Anesiva can successfully develop new products and the degree to which these gain market acceptance. Actual results may differ materially from those contained in the forward-looking statements in this press release. Additional information concerning these and other risk factors is contained in Anesiva's quarterly report on Form 10-Q for the quarter ended September 30, 2006.
Anesiva undertakes no obligation and does not intend to update these forward-looking statements to reflect events or circumstances occurring after this press release. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement.
Anesiva, Inc.
http://www.anesiva.com
"A key attribute of 4975 is its potential to significantly reduce pain and provide additional benefit to patients receiving multimodal analgesia. We were pleased to see that the patients in the knee replacement study who were treated with 4975 showed a trend toward reduced morphine usage to manage their pain," said Daniel J. Gennevois, M.D., senior vice president of clinical development at Anesiva. "Following our successful meeting with the FDA, we now have a clear development pathway for 4975 and are focusing our near-term efforts in two areas-post-surgical pain and pain associated with osteoarthritis-both areas in which 4975 has shown its ability to reduce pain following just a single administration."
All patients in the trial received progressive multimodal analgesia, and despite the multiple medications that patients receive following knee replacement surgeries, they still experience moderate to severe pain. Additionally, post-operatively, all patients in the trial self-administered intravenous morphine via patient controlled analgesia (PCA) pump to achieve satisfactory analgesia for approximately 48-hours following surgery, and a trend toward lower morphine usage was demonstrated in the 4975-treated group versus the placebo-treated group. This is an important finding, as an advantage of 4975 is its potential to reduce the need for opioid drugs, which are well known to have side effects such as sedation, respiratory depression, euphoria, and nausea and vomiting during acute use, and constipation and physical dependence during chronic use. In clinical studies to date, 4975 has not had the side effects often associated with other conventional pain medications and has been shown to be well tolerated. The incidence of treatment-related adverse events (AEs) was generally comparable between the groups with the most frequently reported AEs being localized or peripheral redness and swelling. Most AEs were mild in severity and no patient in the 4975 group withdrew from the study because of an AE.
As was previously reported, the difference in average daily pain scores upon ambulation between the 4975-treated group (n=25) and the placebo group (n=25) on day one was statistically significant (p=0.0273) and showed a relative difference in pain of 24 percent. On a numerical rating scale of zero to 10, the average pain score for the treated group was 5.4 compared with the placebo group's average of 7.1. It is noteworthy that this difference was detected despite all patients being on concomitant morphine. On day 14, the patients' "worst pain in the previous 24-hour period" using the Brief Pain Inventory form showed a relative difference of 34 percent with the average pain scores being 3.9 and 5.9 for the treated group and placebo group, respectively (p=0.0071). This long-lasting analgesic effect may provide benefit to patients receiving a total knee replacement since they must endure an intensive and lengthy rehabilitation period in order to ensure successful function of the new knee. The analysis of additional exploratory efficacy endpoints favored the 4975 group over the placebo group including average daily pain scores at multiple time points: day 1, day 2, days 1-2, days 3-7, days 8-14, days 1-14 and days 3-14. In addition, the measurement of pain interference with activities favored the 4975 group over the placebo group at most of the time points measured.
The Phase 2 study involved 50 knee replacement surgery patients who were randomized to receive either a single dose of 4975 or placebo, which was dripped by syringe into the wound prior to closure. In addition to general anesthesia, concomitant analgesics included a preoperative femoral nerve block, intraoperative bupivacaine via wound infiltration and pre-, intra-, and post-operative intravenous ketorolac. Additionally, post-operatively, patients had the option to self administer intravenous morphine for approximately 48 hours post-surgery. After morphine was discontinued, patients could receive supplemental hydrocodone/acetaminophen as needed to manage their pain.
A follow-on Phase 2 clinical trial in approximately 50 patients undergoing knee replacement surgeries is expected to begin during the first half of 2007. The trial will evaluate a higher dose of 4975 than that used in the previous study. Anesiva plans to initiate a Phase 3 trial in knee replacement surgery patients in the second half of 2007.
Total knee replacement (also known as total knee arthroplasty) is performed in patients with end-stage osteoarthritis of the knee. These patients have disabling pain which imposes severe limitations on their mobility, and knee replacement is performed with the goal of restoring or improving patients' quality of life. There were an estimated 470,000 total knee replacement procedures performed in the United States in 2005, and the number of replacements will continue to grow as the average age of the U.S. population increases and as these individuals conduct more active lives. The American Academy of Orthopedic Surgeons projects that approximately 3.5 million of these procedures will be done each year by 2030.
How 4975 May Address Need for Long-Duration, Well-Tolerated Pain Relief
4975 is long-acting, with the potential to provide pain relief for weeks or months after just a single localized treatment. It is a non-opioid TRPV1 agonist with a unique mechanism of action that provides a long-lasting, localized effect on C-fibers and blocks the transmission of aching, throbbing pain caused by major surgical procedures and end-stage osteoarthritis. Because it selectively acts on pain-sensing nerve endings, 4975 does not affect other nerve fibers necessary for sensory or motor sensations, such as those needed to sense temperature or pressure.
About Anesiva
Anesiva, Inc. is a late-stage biopharmaceutical company that seeks to be the leader in the development and commercialization of novel therapeutic treatments for pain. The company has two drug candidates in development for multiple pain-related indications. A New Drug Application (NDA) has been filed for the most advanced product, Zingo(TM). The second product in the pipeline, 4975, has been shown to reduce pain after only a single administration for weeks to months in multiple settings in numerous mid-stage clinical trials for site-specific, moderate-to-severe pain. Anesiva is based in South San Francisco, CA. For more information about Anesiva's leadership in the development of products for pain management, and an overview of the clinical challenges being addressed by its product candidates, go to http://www.anesiva.com.
Forward-Looking Statements
This press release includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Words such as "expect," "estimate," "project," "budget," "forecast," "anticipate," "intend," "plan," "may," "will," "could," "should," "believes," "predicts," "potential," "continue," and similar expressions are intended to identify such forward-looking statements. Forward- looking statements in this press release include matters that involve known and unknown risks, uncertainties and other factors that may cause actual results, levels of activity, performance or achievements to differ materially from results expressed or implied by this press release. Such risk factors include, among others, whether Anesiva can successfully develop new products and the degree to which these gain market acceptance. Actual results may differ materially from those contained in the forward-looking statements in this press release. Additional information concerning these and other risk factors is contained in Anesiva's quarterly report on Form 10-Q for the quarter ended September 30, 2006.
Anesiva undertakes no obligation and does not intend to update these forward-looking statements to reflect events or circumstances occurring after this press release. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement.
Anesiva, Inc.
http://www.anesiva.com
Alpharma Data Demonstrates Alcohol Does Not Significantly Affect Pharmacokinetics Of KADIAN(R) Capsules
Alpharma Inc. (NYSE: ALO), a leading global specialty pharmaceutical company, presented results of a Phase IV study of KADIAN(R) (morphine sulfate extended-release) Capsules that demonstrate the pharmacokinetics of the long-acting opioid are not significantly affected by the consumption of alcohol. Results of this pharmacokinetic study, which Alpharma conducted in response to a request by the U.S. Food and Drug Administration (FDA) to assess whether alcohol interferes with the extended-release mechanism of action in long-acting opioids, were presented yesterday at the 23rd Annual Meeting of the American Academy of Pain Medicine (AAPM) in New Orleans, LA.
"This study demonstrated that the extended-release properties of KADIAN(R) were maintained even in the presence of a significant quantity of alcohol," says Joseph Stauffer, DO, Vice President, Clinical Research & Medical Affairs, Alpharma Pharmaceuticals Division Inc. "We believe this information is valuable for doctors in their assessment of KADIAN(R), and we will continue to educate clinicians and patients about the appropriate use of KADIAN(R) for moderate-to-severe chronic pain. Like most medications, KADIAN(R) should not be taken with alcohol."
These results indicate that the concomitant use of tested levels of alcohol with KADIAN(R) has no significant impact on mean morphine blood levels or the timing of morphine release.
The company has provided these data to the FDA and any future labeling implications will be determined following the completion of its review.
Study Design
In the open-label, single-dose, three-way crossover pharmacokinetic drug interaction study, 32 healthy adult male volunteers, 21 to 40 years of age, were randomized to receive:
-- KADIAN(R) 100 mg with ethanol (8 ounces of 40 percent alcohol) while fasting;
-- KADIAN(R) 100 mg with ethanol (8 ounces of 40 percent alcohol) while fed;
-- KADIAN(R) 100 mg with 8 ounces of water while fasting;
After the three-way crossover, all subjects then received an immediate- release morphine formulation with 8 ounces of water while fasting, as a reference.
Oral naltrexone hydrochloride was administered 12 hours and 2 hours prior to treatment to counter morphine effects.
There were no serious adverse events reported during the study. Most adverse events were mild to moderate, and one was severe, chest pain. All adverse events resolved before the end of the study.
This study was supported by Alpharma Inc.'s Pharmaceuticals Division, which has a growing franchise in chronic pain treatment.
About KADIAN(R) Capsules
KADIAN(R) (morphine sulfate extended-release) Capsules are an extended- release formulation of morphine sulfate indicated for the management of moderate-to-severe chronic pain, when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. Capsules can be taken once-daily (Q24h) or twice-daily (Q12h), as prescribed, to provide up to 24 hours of pain relief.
Capsules are available in six strengths: 20 mg, 30 mg, 50 mg, 60 mg, 80 mg and 100 mg. The 100 mg capsules are for use in opioid-tolerant patients only. KADIAN(R) offers flexible dosing and administration options that allow physicians to fine-tune titration schedules and tailor treatment for individual patient needs.
KADIAN(R) may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression because respiratory depression, hypotension and profound sedation or coma may result.
KADIAN(R) side effects are generally consistent with those found with other opioids. The most common include drowsiness, constipation, nausea, dizziness and anxiety. Serious adverse reactions that may be associated with KADIAN(R) include respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, low blood pressure and/or shock.
KADIAN(R) Capsules contain an opioid agonist which is a Schedule II controlled substance. KADIAN(R) has an abuse liability similar to other opioids. This should be considered when prescribing or dispensing KADIAN(R).
For complete prescribing information, visit http://www.KADIAN.com.
About Alpharma Inc.
Alpharma Inc. (NYSE: ALO) is a global specialty pharmaceutical company with leadership positions in products for humans and animals. Alpharma is presently active in more than 60 countries. Alpharma has a growing branded franchise in the chronic pain market with its morphine-based extended release KADIAN(R) product. In addition, Alpharma is among the world's leading producers of several specialty pharmaceutical-grade bulk antibiotics and is internationally recognized as a leading provider of pharmaceutical products for poultry and livestock.
Statements made in this release include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements, including those relating to future financial expectations, involve certain risks and uncertainties that could cause actual results to differ materially from those in the forward-looking statements. The 2006 outlook assumes no material adverse event contemplated by the risk factors described in the Company's SEC filings. Information on other significant potential risks and uncertainties not discussed herein may be found in the Company's filings with the Securities and Exchange Commission including its Form 10-K for the year ended December 31, 2005.
Alpharma Inc.
http://www.alpharma.com
"This study demonstrated that the extended-release properties of KADIAN(R) were maintained even in the presence of a significant quantity of alcohol," says Joseph Stauffer, DO, Vice President, Clinical Research & Medical Affairs, Alpharma Pharmaceuticals Division Inc. "We believe this information is valuable for doctors in their assessment of KADIAN(R), and we will continue to educate clinicians and patients about the appropriate use of KADIAN(R) for moderate-to-severe chronic pain. Like most medications, KADIAN(R) should not be taken with alcohol."
These results indicate that the concomitant use of tested levels of alcohol with KADIAN(R) has no significant impact on mean morphine blood levels or the timing of morphine release.
The company has provided these data to the FDA and any future labeling implications will be determined following the completion of its review.
Study Design
In the open-label, single-dose, three-way crossover pharmacokinetic drug interaction study, 32 healthy adult male volunteers, 21 to 40 years of age, were randomized to receive:
-- KADIAN(R) 100 mg with ethanol (8 ounces of 40 percent alcohol) while fasting;
-- KADIAN(R) 100 mg with ethanol (8 ounces of 40 percent alcohol) while fed;
-- KADIAN(R) 100 mg with 8 ounces of water while fasting;
After the three-way crossover, all subjects then received an immediate- release morphine formulation with 8 ounces of water while fasting, as a reference.
Oral naltrexone hydrochloride was administered 12 hours and 2 hours prior to treatment to counter morphine effects.
There were no serious adverse events reported during the study. Most adverse events were mild to moderate, and one was severe, chest pain. All adverse events resolved before the end of the study.
This study was supported by Alpharma Inc.'s Pharmaceuticals Division, which has a growing franchise in chronic pain treatment.
About KADIAN(R) Capsules
KADIAN(R) (morphine sulfate extended-release) Capsules are an extended- release formulation of morphine sulfate indicated for the management of moderate-to-severe chronic pain, when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. Capsules can be taken once-daily (Q24h) or twice-daily (Q12h), as prescribed, to provide up to 24 hours of pain relief.
Capsules are available in six strengths: 20 mg, 30 mg, 50 mg, 60 mg, 80 mg and 100 mg. The 100 mg capsules are for use in opioid-tolerant patients only. KADIAN(R) offers flexible dosing and administration options that allow physicians to fine-tune titration schedules and tailor treatment for individual patient needs.
KADIAN(R) may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression because respiratory depression, hypotension and profound sedation or coma may result.
KADIAN(R) side effects are generally consistent with those found with other opioids. The most common include drowsiness, constipation, nausea, dizziness and anxiety. Serious adverse reactions that may be associated with KADIAN(R) include respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, low blood pressure and/or shock.
KADIAN(R) Capsules contain an opioid agonist which is a Schedule II controlled substance. KADIAN(R) has an abuse liability similar to other opioids. This should be considered when prescribing or dispensing KADIAN(R).
For complete prescribing information, visit http://www.KADIAN.com.
About Alpharma Inc.
Alpharma Inc. (NYSE: ALO) is a global specialty pharmaceutical company with leadership positions in products for humans and animals. Alpharma is presently active in more than 60 countries. Alpharma has a growing branded franchise in the chronic pain market with its morphine-based extended release KADIAN(R) product. In addition, Alpharma is among the world's leading producers of several specialty pharmaceutical-grade bulk antibiotics and is internationally recognized as a leading provider of pharmaceutical products for poultry and livestock.
Statements made in this release include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements, including those relating to future financial expectations, involve certain risks and uncertainties that could cause actual results to differ materially from those in the forward-looking statements. The 2006 outlook assumes no material adverse event contemplated by the risk factors described in the Company's SEC filings. Information on other significant potential risks and uncertainties not discussed herein may be found in the Company's filings with the Securities and Exchange Commission including its Form 10-K for the year ended December 31, 2005.
Alpharma Inc.
http://www.alpharma.com
GlaxoSmithKline And XenoPort Announce Agreement On Late-stage Compound For RLS And Neuropathic Pain
GlaxoSmithKline (GSK) and XenoPort, Inc. (Nasdaq: XNPT) today announced an exclusive agreement to co-develop and commercialise XP13512, a unique prodrug of gabapentin that improves its bioavailability, in the US and other countries worldwide, excluding certain Asian countries. XP13512 is currently in Phase III development for Restless Legs Syndrome (RLS) and in Phase II development for neuropathic pain. Prior clinical trial results have been encouraging.
XP13512 is a patented, new chemical entity that is designed to improve upon the clinical utility of gabapentin by taking advantage of high-capacity transport mechanisms in the gut to improve absorption.
Under the terms of the agreement, XenoPort is entitled to receive an up-front cash payment of ВЈ40 million. XenoPort is also eligible to receive aggregate milestone payments of up to ВЈ34 million for development activities leading up to the NDA filing for RLS, up to ВЈ111million in other potential development and regulatory milestone payments and up to ВЈ153million in potential sales milestone payments based on successful commercialization of XP13512 for RLS and neuropathic pain. In addition to royalties on sales outside the US, XenoPort is entitled to receive tiered, double-digit royalty payments on US sales of XP13512 unless XenoPort elects to co-promote XP13512 with GSK in the US, in which case it will be entitled to participate in a net profit share for XP13512 in the US. If XenoPort decides to co-promote XP13512 in the US, it is also entitled to detail REQUIP products currently in development by GSK, provided they are approved in the US. GSK will have an exclusive right to develop, manufacture and commercialise XP13512 in the US and all countries worldwide except certain Asian countries previously licensed by XenoPort to Astellas Pharma Inc.
In the US, XenoPort will complete the ongoing studies to support RLS development. Subject to positive Phase III clinical data, GSK will file the NDA for RLS for FDA approval. GSK will lead development and registration of XP13512 for all other indications, including neuropathic pain. GSK will also be solely responsible for the manufacture of XP13512 to support its development and commercialization within the licensed territories.
The agreement is subject to review by the US Government under the Hart-Scott-Rodino Act and will become effective after clearing review.
Moncef Slaoui, chairman of R&D, GSK, commented, "This is another important late-stage programme addition to GSK's R&D pipeline. We are pleased to work with XenoPort toward bringing a new treatment alternative for the management of these two important disease areas of RLS and neuropathic pain where there is still such a large unmet need."
Ronald W. Barrett, Ph.D., XenoPort's chief executive officer, stated, "GSK has demonstrated leadership and innovation in educating doctors and patients about the debilitating aspects of RLS and has helped improve the lives of many patients with RLS. We are excited to be collaborating with GSK to advance the development and commercialization of XP13512 and, most importantly, to be creating a new treatment for patients with RLS and neuropathic pain."
Conference Call
XenoPort will host a conference call at 11:00 a.m. Eastern Time today to discuss its agreement with GSK. To access the conference http://www.XenoPort.com
About GlaxoSmithKline
GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies and is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For more information, visit GlaxoSmithKline on the World Wide Web at http://www.gsk.com.
About XenoPort
XenoPort, Inc. is a biopharmaceutical company focused on developing a portfolio of internally discovered product candidates that utilize the body's natural nutrient transport mechanisms to improve the therapeutic benefits of existing drugs. XenoPort's most advanced product candidate, XP13512, is the subject of this announced alliance with GSK. XenoPort also has a second product candidate, XP19986. Positive Phase IIa results have been reported in patients with Gastroesophageal Reflux Disease (GERD) with XP19986.
XenoPort Forward-Looking Statements
This press release contains "forward-looking" statements, including, without limitation, all statements related to our future clinical development program for XP13512 and the timing thereof; the therapeutic and commercial potential of XP13512; future clinical development plans; potential future development and regulatory milestone payments, sales milestone payments, royalty payments and net profit share; and our future clinical trials. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "targeted" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon XenoPort's current expectations. Forward-looking statements involve risks and uncertainties. XenoPort's actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the ability of the company to successfully conduct the clinical trials for XP13512 and the results thereof; the uncertainty of the FDA approval process and other regulatory requirements; the therapeutic and commercial value of XP13512; and our dependence on GSK for aspects of the development, regulatory approval, manufacturing and commercialization of XP13512. These and other risk factors are discussed under the heading "Risk Factors" in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2006, filed with the Securities and Exchange Commission on November 3, 2006. XenoPort expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in the company's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.
GlaxoSmithKline Forward-Looking Statements
Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under 'Risk Factors' in the Operating and Financial Review and Prospects in the company's Annual Report on Form 20-F for 2005.
XenoPort is a registered US trademark.
GlaxoSmithKline
http://www.gsk.com
XP13512 is a patented, new chemical entity that is designed to improve upon the clinical utility of gabapentin by taking advantage of high-capacity transport mechanisms in the gut to improve absorption.
Under the terms of the agreement, XenoPort is entitled to receive an up-front cash payment of ВЈ40 million. XenoPort is also eligible to receive aggregate milestone payments of up to ВЈ34 million for development activities leading up to the NDA filing for RLS, up to ВЈ111million in other potential development and regulatory milestone payments and up to ВЈ153million in potential sales milestone payments based on successful commercialization of XP13512 for RLS and neuropathic pain. In addition to royalties on sales outside the US, XenoPort is entitled to receive tiered, double-digit royalty payments on US sales of XP13512 unless XenoPort elects to co-promote XP13512 with GSK in the US, in which case it will be entitled to participate in a net profit share for XP13512 in the US. If XenoPort decides to co-promote XP13512 in the US, it is also entitled to detail REQUIP products currently in development by GSK, provided they are approved in the US. GSK will have an exclusive right to develop, manufacture and commercialise XP13512 in the US and all countries worldwide except certain Asian countries previously licensed by XenoPort to Astellas Pharma Inc.
In the US, XenoPort will complete the ongoing studies to support RLS development. Subject to positive Phase III clinical data, GSK will file the NDA for RLS for FDA approval. GSK will lead development and registration of XP13512 for all other indications, including neuropathic pain. GSK will also be solely responsible for the manufacture of XP13512 to support its development and commercialization within the licensed territories.
The agreement is subject to review by the US Government under the Hart-Scott-Rodino Act and will become effective after clearing review.
Moncef Slaoui, chairman of R&D, GSK, commented, "This is another important late-stage programme addition to GSK's R&D pipeline. We are pleased to work with XenoPort toward bringing a new treatment alternative for the management of these two important disease areas of RLS and neuropathic pain where there is still such a large unmet need."
Ronald W. Barrett, Ph.D., XenoPort's chief executive officer, stated, "GSK has demonstrated leadership and innovation in educating doctors and patients about the debilitating aspects of RLS and has helped improve the lives of many patients with RLS. We are excited to be collaborating with GSK to advance the development and commercialization of XP13512 and, most importantly, to be creating a new treatment for patients with RLS and neuropathic pain."
Conference Call
XenoPort will host a conference call at 11:00 a.m. Eastern Time today to discuss its agreement with GSK. To access the conference http://www.XenoPort.com
About GlaxoSmithKline
GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies and is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For more information, visit GlaxoSmithKline on the World Wide Web at http://www.gsk.com.
About XenoPort
XenoPort, Inc. is a biopharmaceutical company focused on developing a portfolio of internally discovered product candidates that utilize the body's natural nutrient transport mechanisms to improve the therapeutic benefits of existing drugs. XenoPort's most advanced product candidate, XP13512, is the subject of this announced alliance with GSK. XenoPort also has a second product candidate, XP19986. Positive Phase IIa results have been reported in patients with Gastroesophageal Reflux Disease (GERD) with XP19986.
XenoPort Forward-Looking Statements
This press release contains "forward-looking" statements, including, without limitation, all statements related to our future clinical development program for XP13512 and the timing thereof; the therapeutic and commercial potential of XP13512; future clinical development plans; potential future development and regulatory milestone payments, sales milestone payments, royalty payments and net profit share; and our future clinical trials. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "targeted" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon XenoPort's current expectations. Forward-looking statements involve risks and uncertainties. XenoPort's actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the ability of the company to successfully conduct the clinical trials for XP13512 and the results thereof; the uncertainty of the FDA approval process and other regulatory requirements; the therapeutic and commercial value of XP13512; and our dependence on GSK for aspects of the development, regulatory approval, manufacturing and commercialization of XP13512. These and other risk factors are discussed under the heading "Risk Factors" in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2006, filed with the Securities and Exchange Commission on November 3, 2006. XenoPort expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in the company's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.
GlaxoSmithKline Forward-Looking Statements
Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under 'Risk Factors' in the Operating and Financial Review and Prospects in the company's Annual Report on Form 20-F for 2005.
XenoPort is a registered US trademark.
GlaxoSmithKline
http://www.gsk.com
Opioid Prescribing At Forefront Of Pain Medicine Meeting
Opioid therapy, opioid prescribing and prescription drug diversion were provoking topics at the 23rd annual meeting of the American Academy of Pain Medicine (AAPM) at the Hilton New Orleans Riverside Hotel/Morial Convention Center, February 7-10, 2007.
Opioid treatment is an essential component of pain care for many patients and can be delivered safely and effectively, according to Frederick Burgess, M.D., Ph.D., AAPM president, who estimates that 20 to 60 million Americans live with chronic pain.
Prescription Drug Diversion
A common goal of both physicians and law enforcement is to maintain an appropriate balance between preventing the illegal diversion of drugs while safeguarding the needs of legitimate pain patients, according to the experts speaking at the "Pain Medicine and Law Enforcement: Achieving a Team Approach" session.
"Physicians have nothing to fear from the Drug Enforcement Administration (DEA) in their legitimate practice of medicine," says Mark W. Caverly, who is chief of the liaison and policy section in the DEA Office of Diversion Control. "The DEA's guiding principle is to prevent the diversion and abuse of pharmaceutical controlled substances without impacting the ability of patients with legitimate need to have full access to pain relief as prescribed by their physician. The DEA's responsibility is to enforce the law, not dictate the practice of medicine," concludes Caverly, who will represent the DEA during the Pain Medicine and Law Enforcement session.
Caverly also discussed the legal standards of prescribing as set forth in the Controlled Substances Act, the proposed rule to allow multiple prescriptions for schedule II controlled substances, and upcoming policy/regulation topics.
In the same session, John Burke, who is president of the National Association of Drug Diversion Investigators, addressed prescription drugs of abuse and related diversion scams.
"Knowing what the current drug diversion scams are can help physicians decide who is trying to take advantage of them," says Burke, commander of the Warren County Drug Task Force in the Cincinnati area of southwest Ohio. "The vast majority of patients are not drug seekers and that is where the balance comes in. We do not want to deprive legitimate patients effective pain relief through legally prescribed medications because of the acts of a relative few."
"Today, pain medicine specialists are concentrating on the development of the best scientific and clinical protocols for opioid use," Dr. Burgess comments. Opioid treatment was addressed at the meeting in a number of scientific sessions, poster presentations and scientific abstracts.
Other Program Highlights:
Cannabinoids - A New Class of Analgesics
Four Decades of Neuromodulation
Pain Medicine and Law Enforcement: Achieving a Team Approach
Medical Conditions for Patients With Pain After Natural Disaster
Opioids: Good or Bad?
Ethical Medical Practice and Managed Care: An Oxymoron?
Breaking Concepts in Diagnosis and Treatment of Complex Regional Pain Syndromes
"The AAPM annual meeting is a gathering of pain medicine experts from across the country who spend three days together sharing information about the latest research, patient care, and regulatory issues that affect the practice of Pain Medicine," says Dr. Burgess.
###
Founded in 1983, AAPM is the medical specialty society representing physicians practicing in the field of pain medicine. The Academy is involved in education, training, advocacy and research in the specialty of pain medicine. Information is available on the practice of pain medicine at http://www.painmed.org/.
Contact: Amy Jenkins
American Academy of Pain Medicine
Opioid treatment is an essential component of pain care for many patients and can be delivered safely and effectively, according to Frederick Burgess, M.D., Ph.D., AAPM president, who estimates that 20 to 60 million Americans live with chronic pain.
Prescription Drug Diversion
A common goal of both physicians and law enforcement is to maintain an appropriate balance between preventing the illegal diversion of drugs while safeguarding the needs of legitimate pain patients, according to the experts speaking at the "Pain Medicine and Law Enforcement: Achieving a Team Approach" session.
"Physicians have nothing to fear from the Drug Enforcement Administration (DEA) in their legitimate practice of medicine," says Mark W. Caverly, who is chief of the liaison and policy section in the DEA Office of Diversion Control. "The DEA's guiding principle is to prevent the diversion and abuse of pharmaceutical controlled substances without impacting the ability of patients with legitimate need to have full access to pain relief as prescribed by their physician. The DEA's responsibility is to enforce the law, not dictate the practice of medicine," concludes Caverly, who will represent the DEA during the Pain Medicine and Law Enforcement session.
Caverly also discussed the legal standards of prescribing as set forth in the Controlled Substances Act, the proposed rule to allow multiple prescriptions for schedule II controlled substances, and upcoming policy/regulation topics.
In the same session, John Burke, who is president of the National Association of Drug Diversion Investigators, addressed prescription drugs of abuse and related diversion scams.
"Knowing what the current drug diversion scams are can help physicians decide who is trying to take advantage of them," says Burke, commander of the Warren County Drug Task Force in the Cincinnati area of southwest Ohio. "The vast majority of patients are not drug seekers and that is where the balance comes in. We do not want to deprive legitimate patients effective pain relief through legally prescribed medications because of the acts of a relative few."
"Today, pain medicine specialists are concentrating on the development of the best scientific and clinical protocols for opioid use," Dr. Burgess comments. Opioid treatment was addressed at the meeting in a number of scientific sessions, poster presentations and scientific abstracts.
Other Program Highlights:
Cannabinoids - A New Class of Analgesics
Four Decades of Neuromodulation
Pain Medicine and Law Enforcement: Achieving a Team Approach
Medical Conditions for Patients With Pain After Natural Disaster
Opioids: Good or Bad?
Ethical Medical Practice and Managed Care: An Oxymoron?
Breaking Concepts in Diagnosis and Treatment of Complex Regional Pain Syndromes
"The AAPM annual meeting is a gathering of pain medicine experts from across the country who spend three days together sharing information about the latest research, patient care, and regulatory issues that affect the practice of Pain Medicine," says Dr. Burgess.
###
Founded in 1983, AAPM is the medical specialty society representing physicians practicing in the field of pain medicine. The Academy is involved in education, training, advocacy and research in the specialty of pain medicine. Information is available on the practice of pain medicine at http://www.painmed.org/.
Contact: Amy Jenkins
American Academy of Pain Medicine
Avoid Back Injury At Work By Taking More Breaks, Study Says
Workers who lift for a living need to take longer or more frequent breaks than they now do to avoid back injury, according to a new study at Ohio State University .
The study also suggests that people who are new on the job need to take breaks even more often than experienced workers, and that the risk of injury is higher at the end of a work shift.
People who participated in the study lifted boxes onto conveyor belts for eight hours, while researchers measured the amount of oxygen that was reaching the muscles in their lower back.
The oxygen level indicated how hard the muscles were working, and whether they were becoming fatigued, explained William Marras, professor of industrial welding and systems engineering at Ohio State. His research and others' has shown that muscle fatigue is linked to back injury.
The study, which appeared in a recent issue of the journal Clinical Biomechanics, is the first to examine what happens to muscle oxygenation over a full workday.
Despite the fact that the study participants were performing the same job at the same pace all day, their back muscles needed more oxygen as the day went on. Taking a half-hour lunch break helped their muscles recover from the morning's exertion, but once they started working again, their oxygen needs rose steeply and kept climbing throughout the afternoon.
"That was alarming to us, because it means that their muscles were becoming fatigued much faster during the afternoon, and we know that fatigue increases the risk of back injury," Marras said.
Two 15-minute breaks, one mid-morning and the other mid-afternoon, helped muscles recover a little, but not as much as the half-hour lunch.
"This tells us two things," Marras said. "First, rest is good -- a half-hour break does a good job of helping muscles recover. But it also tells us that people are especially at risk for back injury at the end of the day, and the only way to counteract that effect is with more breaks as the day goes on."
Ten people participated in the study, six of whom had at least one year's experience in a job that requires lifting, such as stocking store shelves. The other four were considered novice lifters.
One person would lift a box from a waist-high stand and set it on a chest-high conveyor belt in Marras' lab, which simulates a typical shipping center. The box then traveled down the belt to the other person, who would lift it and set it on another conveyor belt. They lifted boxes of three different weights -- two pounds, 11 pounds, and 26 pounds -- and they worked for the entire eight hours, except for the half-hour lunch break and the two 15-minute breaks.
Each person wore a Lumbar Motion Monitor, a device that Marras designed to measure the movement of the spine. They also wore oximeters on their lower back -- devices that measured the oxygen level of their muscles through the skin. Just like the pulse oximeters that doctors clip to a patient's finger, these sensors use an LED light to detect the flush of color to the skin when blood carries oxygen to the tissues underneath.
Study coauthor Gang Yang, a medical doctor who is now earning a doctoral degree in biomechanics at Ohio State, said that the researchers' top priority was making sure the subjects didn't grow fatigued enough to become injured during the study. The heaviest box they had to lift, 26 pounds, weighed less than half as much as the loads that some workers are routinely required to lift in industry.
In Clinical Biomechanics, the researchers detailed the oxygen levels in the muscles of the typical study participant. During the first two hours of lifting, the oxygenation level gradually increased until it reached 11 percent above resting level. During hours two to four, it rose to 13 percent. It returned to resting level during lunch, but immediately rose 11 percent as the people started lifting again during hours four to six. During the last two hours of the day, oxygenation rose to its highest level -- 16 percent above resting level.
"Because the oxygen demand at the end of the day was so much higher, that's when we'd expect people to get hurt on the job," Marras said. "And the data I see coming out of industry bear that out -- people tend to hurt their back toward the end of a shift."
Meanwhile, data from the Lumbar Motion Monitor showed that the participants used their muscles differently as they became fatigued -- a finding that meshes with Marras' previous work. He's found that when people's back muscles begin to hurt, they tense up, and try to lift with other muscles that don't hurt as much.
"Now because of this study, we have a clinical reason for why that's happening. It's because the muscles are becoming fatigued, because they have such a high demand for oxygen," Marras said.
Tensing muscles prevents proper blood flow, so the muscles are even further deprived of oxygen. And using different muscles to lift may lessen pain at first, but it increases the stress on the joints and the spine, and increases risk of serious injury in the long run.
"When that happens, it's like the muscles fight each other," Marras said. "You have back muscles that fight the abdominal muscles, and when they both contract, it's like a seesaw effect, except you're pulling down on both ends, and your spine is in the middle."
The researchers found that participants who had never lifted for a living let their muscles tense up during the study. Their muscles also needed more oxygen than the experienced lifters, who generally relaxed their muscles and used the proper muscles for lifting.
"The bottom line is that it's much more costly from a physiological standpoint for novices to do the same work as experienced people," Marras said.
Low back pain is the most common and most costly musculoskeletal disorder in the American workplace. According to the U.S. Bureau of Labor Statistics, in 2002 there were more than 345,000 back injuries requiring time away from work. A 2004 study by Harvard Medical School and Massachusetts General Hospital found that back pain results in over 100 million lost work days per year. And a Duke University Medical Center Study found that in 1998, total health care expenditures incurred by people with back pain in the United States reached $90.7 billion.
Taking half-hour breaks instead of the standard 15 minutes might help reduce back injury, Marras said, although he acknowledged that such long breaks might not be practical in industry. He pointed to other studies, however, which showed that shorter breaks, taken more frequently, have a similar positive effect.
###
Marras and Yang's coauthors on the study included former graduate students Anne-Marie Chany, now at Columbus Children's Hospital, and Julia Parakkat, now at Wright-Patterson Air Force Base; and Deborah Burr, associate professor of biostatistics at the University of Florida.
This study was funded by the National Institute for Occupational Safety and Health.
Written by Pam Frost Gorder, (614) 292-9475; Gorder.1@osu.edu
Contact: William Marras
Ohio State University
The study also suggests that people who are new on the job need to take breaks even more often than experienced workers, and that the risk of injury is higher at the end of a work shift.
People who participated in the study lifted boxes onto conveyor belts for eight hours, while researchers measured the amount of oxygen that was reaching the muscles in their lower back.
The oxygen level indicated how hard the muscles were working, and whether they were becoming fatigued, explained William Marras, professor of industrial welding and systems engineering at Ohio State. His research and others' has shown that muscle fatigue is linked to back injury.
The study, which appeared in a recent issue of the journal Clinical Biomechanics, is the first to examine what happens to muscle oxygenation over a full workday.
Despite the fact that the study participants were performing the same job at the same pace all day, their back muscles needed more oxygen as the day went on. Taking a half-hour lunch break helped their muscles recover from the morning's exertion, but once they started working again, their oxygen needs rose steeply and kept climbing throughout the afternoon.
"That was alarming to us, because it means that their muscles were becoming fatigued much faster during the afternoon, and we know that fatigue increases the risk of back injury," Marras said.
Two 15-minute breaks, one mid-morning and the other mid-afternoon, helped muscles recover a little, but not as much as the half-hour lunch.
"This tells us two things," Marras said. "First, rest is good -- a half-hour break does a good job of helping muscles recover. But it also tells us that people are especially at risk for back injury at the end of the day, and the only way to counteract that effect is with more breaks as the day goes on."
Ten people participated in the study, six of whom had at least one year's experience in a job that requires lifting, such as stocking store shelves. The other four were considered novice lifters.
One person would lift a box from a waist-high stand and set it on a chest-high conveyor belt in Marras' lab, which simulates a typical shipping center. The box then traveled down the belt to the other person, who would lift it and set it on another conveyor belt. They lifted boxes of three different weights -- two pounds, 11 pounds, and 26 pounds -- and they worked for the entire eight hours, except for the half-hour lunch break and the two 15-minute breaks.
Each person wore a Lumbar Motion Monitor, a device that Marras designed to measure the movement of the spine. They also wore oximeters on their lower back -- devices that measured the oxygen level of their muscles through the skin. Just like the pulse oximeters that doctors clip to a patient's finger, these sensors use an LED light to detect the flush of color to the skin when blood carries oxygen to the tissues underneath.
Study coauthor Gang Yang, a medical doctor who is now earning a doctoral degree in biomechanics at Ohio State, said that the researchers' top priority was making sure the subjects didn't grow fatigued enough to become injured during the study. The heaviest box they had to lift, 26 pounds, weighed less than half as much as the loads that some workers are routinely required to lift in industry.
In Clinical Biomechanics, the researchers detailed the oxygen levels in the muscles of the typical study participant. During the first two hours of lifting, the oxygenation level gradually increased until it reached 11 percent above resting level. During hours two to four, it rose to 13 percent. It returned to resting level during lunch, but immediately rose 11 percent as the people started lifting again during hours four to six. During the last two hours of the day, oxygenation rose to its highest level -- 16 percent above resting level.
"Because the oxygen demand at the end of the day was so much higher, that's when we'd expect people to get hurt on the job," Marras said. "And the data I see coming out of industry bear that out -- people tend to hurt their back toward the end of a shift."
Meanwhile, data from the Lumbar Motion Monitor showed that the participants used their muscles differently as they became fatigued -- a finding that meshes with Marras' previous work. He's found that when people's back muscles begin to hurt, they tense up, and try to lift with other muscles that don't hurt as much.
"Now because of this study, we have a clinical reason for why that's happening. It's because the muscles are becoming fatigued, because they have such a high demand for oxygen," Marras said.
Tensing muscles prevents proper blood flow, so the muscles are even further deprived of oxygen. And using different muscles to lift may lessen pain at first, but it increases the stress on the joints and the spine, and increases risk of serious injury in the long run.
"When that happens, it's like the muscles fight each other," Marras said. "You have back muscles that fight the abdominal muscles, and when they both contract, it's like a seesaw effect, except you're pulling down on both ends, and your spine is in the middle."
The researchers found that participants who had never lifted for a living let their muscles tense up during the study. Their muscles also needed more oxygen than the experienced lifters, who generally relaxed their muscles and used the proper muscles for lifting.
"The bottom line is that it's much more costly from a physiological standpoint for novices to do the same work as experienced people," Marras said.
Low back pain is the most common and most costly musculoskeletal disorder in the American workplace. According to the U.S. Bureau of Labor Statistics, in 2002 there were more than 345,000 back injuries requiring time away from work. A 2004 study by Harvard Medical School and Massachusetts General Hospital found that back pain results in over 100 million lost work days per year. And a Duke University Medical Center Study found that in 1998, total health care expenditures incurred by people with back pain in the United States reached $90.7 billion.
Taking half-hour breaks instead of the standard 15 minutes might help reduce back injury, Marras said, although he acknowledged that such long breaks might not be practical in industry. He pointed to other studies, however, which showed that shorter breaks, taken more frequently, have a similar positive effect.
###
Marras and Yang's coauthors on the study included former graduate students Anne-Marie Chany, now at Columbus Children's Hospital, and Julia Parakkat, now at Wright-Patterson Air Force Base; and Deborah Burr, associate professor of biostatistics at the University of Florida.
This study was funded by the National Institute for Occupational Safety and Health.
Written by Pam Frost Gorder, (614) 292-9475; Gorder.1@osu.edu
Contact: William Marras
Ohio State University
Trial Comparison Will Help In Treatment Of Arthritis
Incidence of upper gastrointestinal clinical events in patients with arthritis on the COX-2 inhibitor etoricoxib are fewer than in those patients on the NSAID* diclofenac, according to an Article in this week's issue of The Lancet. This information will assist patients with arthritis and their physicians in making decisions about pain management.
NSAIDS are often taken long term by arthritis patients. However, they significantly increase the risk of upper gastrointestinal clinical events such as bleeding ulcers. The incidences of upper gastrointestinal clinical events have been shown to be significantly less with COX-2 than traditional NSAIDS. However, previous trials have not simulated standard clinical practice because gastrointestinal protective therapies - eg, proton pump inhibitors (PPIs) - were not allowed.
Loren Laine (University of Southern California Keck School of Medicine, Los Angeles, USA) and colleagues analyse data from three randomised trials from the MEDAL (Multinational Etoricoxib and Diclofenac Arthritis Long-term) programme†to assess the effects of COX-2 inhibitors versus traditional NSAIDS on upper gastrointestinal outcomes in a setting that simulates real-world practice, in which patients with gastrointestinal risk factors were encouraged to use protective PPI therapy and those with cardiovascular risk were encouraged to take low-dose aspirin. Overall, upper gastrointestinal clinical events were significantly less common with etoricoxib than with diclofenac, but not in the more serious complicated events‡. The treatment effects did not differ significantly in individuals using PPIs or aspirin.
The authors conclude: "The results of the MEDAL programme provide new information about upper gastrointestinal clinical events and symptoms to assist arthritis patients and their physicians to make decisions regarding NSAID use."
In an accompanying Comment, Joost Drenth and Freek Verheugt (Radboud University Nijmegen, Netherlands) state: "Though eterocoxib reduced upper gastrointestinal events, the effect was only small as 259 patients need to be treated to prevent one uncomplicated gastrointestinal event. The alternative, addition of a PPI to standard NSAID might be less expensive, potentially less cardiotoxic, and advantageous in terms of reducing dyspepsia, but here confirmation needs a randomised trial." (Quote by email; not in published paper)
###
Professor Loren Laine, University of Southern California Keck School of Medicine, Los Angeles, USA.
Comment Professor Joost Drenth, Radboud University Nijmegen, Netherlands. Contact: Joe Santangelo
Lancet
NSAIDS are often taken long term by arthritis patients. However, they significantly increase the risk of upper gastrointestinal clinical events such as bleeding ulcers. The incidences of upper gastrointestinal clinical events have been shown to be significantly less with COX-2 than traditional NSAIDS. However, previous trials have not simulated standard clinical practice because gastrointestinal protective therapies - eg, proton pump inhibitors (PPIs) - were not allowed.
Loren Laine (University of Southern California Keck School of Medicine, Los Angeles, USA) and colleagues analyse data from three randomised trials from the MEDAL (Multinational Etoricoxib and Diclofenac Arthritis Long-term) programme†to assess the effects of COX-2 inhibitors versus traditional NSAIDS on upper gastrointestinal outcomes in a setting that simulates real-world practice, in which patients with gastrointestinal risk factors were encouraged to use protective PPI therapy and those with cardiovascular risk were encouraged to take low-dose aspirin. Overall, upper gastrointestinal clinical events were significantly less common with etoricoxib than with diclofenac, but not in the more serious complicated events‡. The treatment effects did not differ significantly in individuals using PPIs or aspirin.
The authors conclude: "The results of the MEDAL programme provide new information about upper gastrointestinal clinical events and symptoms to assist arthritis patients and their physicians to make decisions regarding NSAID use."
In an accompanying Comment, Joost Drenth and Freek Verheugt (Radboud University Nijmegen, Netherlands) state: "Though eterocoxib reduced upper gastrointestinal events, the effect was only small as 259 patients need to be treated to prevent one uncomplicated gastrointestinal event. The alternative, addition of a PPI to standard NSAID might be less expensive, potentially less cardiotoxic, and advantageous in terms of reducing dyspepsia, but here confirmation needs a randomised trial." (Quote by email; not in published paper)
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Professor Loren Laine, University of Southern California Keck School of Medicine, Los Angeles, USA.
Comment Professor Joost Drenth, Radboud University Nijmegen, Netherlands. Contact: Joe Santangelo
Lancet
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