March 25
-- Anesiva, Inc. today announced the initiation of a pivotal Phase 3 trial evaluating Adlea(TM), its long-acting, non-opioid analgesic drug candidate, in patients following bunionectomy surgery. The multicenter, double-blind, placebo-controlled trial will evaluate the efficacy and safety of Adlea in reducing post-surgical pain in patients undergoing a bunionectomy procedure. Adlea, which is designed to provide pain relief for weeks to months after a single local application, has already demonstrated statistically significant pain reduction in this clinical setting.
A bunionectomy is a surgical procedure that is performed to align the bones of the big toe joint by removing a bunion, which is an enlargement of the joint at the base of the big toe. An estimated 292,000 bunionectomy surgeries are performed in the U.S. each year.
"Because bunionectomies are often performed as out-patient procedures, patients are responsible for their own pain management following surgery. Adlea could fill an important need since it does not require repeated administrations after the initial application during surgery," said Dr. Eric L. Diamond, a podiatrist practicing in Maryland who is an investigator on the Phase 3 study and who also participated in a Phase 2 study of Adlea in bunionectomy surgery. "Furthermore, because Adlea is administered at the surgical site, its effects are targeted. In contrast to systemic pain medications such as opioids, Adlea appears to avoid potentially serious side effects on cognitive function and other organs or muscle groups. This profile affords it the potential to be safely used in conjunction with, and possibly reduce the need for, other pain medications."
The trial, to be conducted in the U.S., will enroll approximately 300 patients undergoing bunionectomy surgery. Patients will be randomized to receive either a single 1.0 mg dose of Adlea or placebo into the surgical site prior to closure. The primary efficacy endpoint is a time-weighted pain score (using a standard 0 - 10 numerical rating system of pain intensity) from four to 32 hours post-surgery. The study will also evaluate rescue opioid consumption at prespecified timepoints during the first two weeks following surgery. Additional patient follow-up will occur at two and four weeks after surgery. The safety of Adlea in this setting will be evaluated.
"We are encouraged by the positive results Adlea has already shown in mid-stage clinical trials for pain management following various surgeries, including bunionectomy. We are optimistic that this Phase 3 trial will further demonstrate Adlea's effectiveness in a multi-modal therapeutic regimen for post-surgical pain," said John P. McLaughlin, chief executive officer of Anesiva. "We plan to initiate an additional Phase 3 trial evaluating Adlea in patients undergoing total knee replacement surgery as part of an initial registration strategy for the use of Adlea in the management of pain following orthopedic surgeries." Top-line data from the Adlea Phase 3 trials are expected by year-end 2008.
Two prior randomized, double-blind, placebo-controlled Phase 2 bunionectomy trials evaluating the use of Adlea to reduce post-surgical pain yielded favorable results. The first was an exploratory study that suggested Adlea at the 1.0 mg dose level to be used in the Phase 3 trial was active relative to placebo. A larger (n=185) Phase 2 trial evaluated three dose levels of Adlea versus placebo. Dose response was demonstrated and, at the 1.0 mg dose level, the Adlea-treated group demonstrated statistically significantly less pain following surgery, and a significantly lower proportion of patients required rescue medication relative to placebo. Evaluations in other dose groups favored Adlea over placebo. Adlea was well tolerated in these studies and adverse events were comparable for placebo and Adlea treated patients.
Adlea is a long-acting, non-opioid drug with the potential to provide pain relief for weeks to months after just a single localized treatment. Its novel mechanism of action results in site-specific efficacy intended to avoid the unwanted side effects associated with systemically administered analagesic drugs.
Adlea is a highly purified form of capsaicin (derived from chili peppers) that acts on C nerve fibers, which transmit long-term pain, by binding to and desensitizing the TRPV1 pain receptors. This leads to a prolonged, reversible and localized desensitization of the pain fibers. The drug generally has a short half-life of 1 to 2 hours. It is undetectable in blood sample analyses after 24 hours.
Adlea's short duration of systemic exposure (hours) relative to the long duration of analgesia (weeks to months) may offer a safe, additive treatment option in the management of post-surgical orthopedic pain. Importantly, the prolonged analgesic effect resulting from localized administration of Adlea does not seem to be associated with the systemic side effects commonly associated with opioids (respiratory depression, nausea/vomiting, sedation, disorientation, physical dependence, and the risk of addiction), or with NSAIDs (gastrointestinal and renal toxicities, and impaired clotting) or COX-2 inhibitors (cardiovascular risks and renal toxicity).
Adlea is also in clinical development for the treatment of pain associated with moderate to severe osteoarthritis. In an exploratory trial in this setting, Adlea provided sustained pain reduction as compared to baseline over the twelve week study period.
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