Date: 2016-05-02
Type of information: Results
phase: 2-3
Announcement: results
Company: Regeneron Pharmaceuticals (USA - NY)
Product: fasinumab
Action
mechanism: monoclonal antibody. Fasinumab is a fully human monoclonal antibody against Nerve Growth Factor (NGF) that was designed to reduce pain sensitization in neurons. Preclinical experiments indicate that fasinumab specifically binds to NGF and blocks NGF activity, and that fasinumab does not bind to or block cell signaling for closely related neurotrophins (NT) such as NT-3, NT-4 or BDNF (brain-derived neurotrophic factor). The FDA placed fasinumab and other investigational agents against NGF on partial clinical hold in December 2012 due to reports of sympathetic nervous system toxicity in mature animals being treated with other anti-NGFs. Fasinumab is no longer on clinical hold by the FDA. A Phase 2b/3 study in pain due to osteoarthritis initiated in mid-2015, and an additional Phase 3 trial of greater than 16 weeks is expected to begin in the first half of 2016.
Disease: moderate-to-severe osteoarthritis pain of the hip or knee
Therapeutic area: Rheumatic diseases - Inflammatory diseases
Country: USA
Trial details:
Latest
news: * On May 2, 2016, Regeneron Pharmaceuticals announced positive topline results from a placebo-controlled Phase 2/3 study evaluating fasinumab in patients with moderate-to-severe osteoarthritis pain of the hip or knee who have a history of inadequate pain relief or intolerance to current analgesic therapies. At 16 weeks, patients treated with all four doses of fasinumab demonstrated a statistically significant improvement in pain relief, the primary endpoint of the study, as well as improvements in the secondary measure evaluating physical function. The U.S. study enrolled 421 adult patients with moderate-to-severe osteoarthritis of the hip or knee who had a history of inadequate pain relief or intolerance to acetaminophen, and at least one oral nonsteroidal anti-inflammatory drug (NSAID) and an opioid. Patients in the study were experiencing significant pain at baseline with an average pain score of 6.3 on a 10-point scale. Patients were evaluated for pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in addition to other measures. Patients were randomized to one of five treatment groups in a 1:1:1:1:1 fashion: fasinumab 1mg, 3mg, 6mg, 9mg, or placebo, all delivered subcutaneously every 4 weeks through week 12, with the primary efficacy measured at week 16. Following week 16, patients are being studied for an additional 20 weeks off treatment. On the primary endpoint, fasinumab-treated patients reported less pain at 16 weeks when compared to placebo on the 10-point WOMAC subscale for pain. Results for each of the dose groups are noted below. The safety analysis includes all results at the time of the primary efficacy analysis; complete data will be reported when all patients complete the full 36 weeks. Overall incidence of adverse events, including serious and severe events, was similar across the fasinumab groups and placebo. As expected with antibodies to NGF, there was an increase in certain neuro-musculoskeletal adverse events in the fasinumab treatment groups (17 percent combined fasinumab; 6 percent placebo) including arthralgia, paraesthesia, hypoaesthesia, and peripheral edema. Because of prior concerns with other anti-NGF therapies regarding the possible risk of joint damage, the study incorporated extensive imaging and analyses at baseline and during the study, of index and non-index joints, with particular focus on subchondral insufficiency fractures (SIF), osteonecrosis (ON) and rapidly progressive osteoarthritis (RPOA). Approximately 2 percent of screened subjects were excluded from participation based on findings of SIF or ON on baseline imaging exams. During the study period there were no cases of ON, there was 1 case of SIF in placebo, 0, 2, 0 and 4 cases of SIF in the 1mg, 3mg, 6mg, and 9mg fasinumab dose groups respectively, and 1 case of RPOA in each of the 3mg, 6mg, and 9mg fasinumab dose groups. A modest increase in the lab value for bone-specific alkaline phosphatase, a marker of osteoblast activity, was noted in fasinumab-treated patients; there was no increase in liver ALT and AST enzymes. Regeneron Pharmaceuticals plans to present detailed results at an upcoming medical congress. The company is also looking forward to continuing fasimab phase 3 program.
