The FDA has placed a clinical hold on the phase 2b study of fasinumab (Regeneron Pharmaceuticals, Inc./Teva Pharmaceutical Industries Ltd.) in patients with chronic low back pain.
Fasinumab is an investigational nerve growth factor antibody in clinical development for osteoarthritis pain and chronic low back pain. The FDA requested an amendment of the study protocol after observing a case of adjudicated arthropathy in a patient receiving high-dose fasinumab who had advanced osteoarthritis at study entry. As a result of the FDA decision, Regeneron completed an unplanned interim review of results and has stopped dosing in the study.
The unplanned analysis showed clear evidence of efficacy with improvement in pain scores in all fasinumab groups compared with placebo at the eight-week and 12-week time points (nominal P < 0.01). Preliminary safety results are generally consistent with what has been previously reported with the class. The phase 2b chronic low back pain study enrolled approximately 70% of the targeted 800 patients in four dose groups: placebo, 6 mg subcutaneously monthly; 9 mg subcutaneously monthly; and 9 mg intravenously every two months. Regeneron has notified health authorities and study investigators about the decision. Patients will continue to be followed for up to 36 weeks.
Based on these results, Regeneron and Teva plan to design a pivotal phase 3 study in chronic low back pain that excludes patients with advanced osteoarthritis. The companies plan to submit a pivotal program plan for review with the FDA and other health authorities.
Previously, 16-week positive results were reported from the fasinumab phase 2/3 osteoarthritis pain study in 421 patients. Patients received their last dose at 12 weeks and a follow-up analysis occurred at 36 weeks. The study incorporated extensive imaging and analyses at baseline and during the study of index and nonindex joints, with particular focus on arthropathies, including subchondral insufficiency fractures, osteonecrosis, and rapidly progressive osteoarthritis. At the 36-week analysis, the incidence of adjudicated arthropathies was found to be potentially dose-dependent, with a higher rate of patients experiencing arthropathies in the higher dose groups (12% [9 mg], 7% [6 mg], 5% [3 mg], 2% [1 mg], and 1% [placebo]). Based on these data, the companies are planning to advance only lower doses in the ongoing fasinumab osteoarthritis pivotal phase 3 program, subject to discussion with the FDA and other health authorities.
Updated data from the osteoarthritis pain phase 2/3 study and the chronic low back pain phase 2b study will be presented at upcoming medical congresses.
"We are making data-driven decisions on phase 3 fasinumab dosing that we believe will maximize potential benefit for patients in need, while minimizing the likelihood of side effects," said George D. Yancopoulos, MD, PhD, Chief Scientific Officer at Regeneron and President of Regeneron Laboratories.
Regeneron and Teva are collaborating on the global development and commercialization of fasinumab. Under a separate agreement with Regeneron, Mitsubishi Tanabe Pharma has exclusive development and commercial rights to fasinumab in Japan, Korea, and nine other Asian countries.
Source: Regeneron; October 17, 2016.