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
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