Anesiva, Inc (SOUTH SAN FRANCISCO, California), a publicly-held, late-stage biopharmaceutical company focused on the development and commercialization of novel therapeutic treatments for pain management, announced preliminary, long-term, follow-up results from a phase II study showing that treatment with Adleaâ„¢ (formerly 4975) in patients with moderate-to-severe osteoarthritis (OA) of the knee produced substantial pain reduction that lasted for up to 12 weeks.

In the study, 55 patients with OA of the knee were randomized to receive either a single injection of 1 mg of Adlea (n=36) or  three stepped ascending weekly doses totaling 1 mg of Adlea (n=19).  Prior to treatment, approximately 75% of the patients  had moderate pain at baseline, while the other 25% had severe or extreme pain.  Patients treated with Adlea demonstrated a 61% reduction in mean pain intensity from baseline to week 1, and the analgesic effect was sustained at all subsequent weeks to the last scheduled in-clinic assessment at week 8, at which time a 64% reduction in pain from baseline was reported. At week 12, pain reduction was sustained. A cohort of 50 patients showed a 65% reduction from baseline pain scores. Forty-two percent of the patients reported "no pain," 44% had "mild pain," and only 14% reported "moderate" or "severe" pain. The lengthy duration of clinical benefit is consistent with Adlea's known mechanism of action that suggests treatment  administered as a single injection or stepped doses leads to sustainable pain relief for 12 weeks in patients suffering from moderate-to-severe knee OA pain.

Adlea is a long-acting, nonopioid agonist of TRPV1 (the transient receptor potential vanilloid 1, formerly known as vanilloid receptor 1 or VR1), a ligand-gated ion channel activated by agonists, such as capsaicin and other factors such as heat and acidosis. The TRPV1 agonist 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 OA. Because it selectively acts on pain-sensing nerve endings, Adlea does not affect other nerve fibers necessary for sensory or motor sensations, such as those needed to sense temperature or pressure. In clinical studies to date, Adlea has also been shown to be well tolerated.

Pharmacokinetic studies showed that when Adlea is locally administered to the site of pain in a single treatment course, there appears to be limited systemic exposure. Its short duration of systemic exposure (hours) relative to the long duration of analgesia (12 weeks) is particularly important in the typically elderly patient population and may potentially offer a safer treatment option for  the management of chronic OA pain. The prolonged analgesic effect resulting from a single or stepped localized dose administration of Adlea does not seem to be associated with the systemic side effects  that commonly result from treatment with NSAIDs (gastrointestinal and renal toxicities and impaired clotting), COX-2 inhibitors (cardiovascular risks and renal toxicity), or opioids (respiratory depression, nausea and/or vomiting, sedation, disorientation, physical dependence, and the risk of addiction).

Anesiva  plans  to advance Adlea into late-stage trials in various indications this summer, including a phase II/III trial for OA of the knee.

—A. Techman

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