The Food and Drug Administration (FDA) Joint Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee voted 1 in favor and 19 against on the question of whether the proposed risk evaluation and mitigation strategy (REMS) for tanezumab 2.5mg would ensure its benefits outweigh its risks for the treatment of moderate to severe osteoarthritis (OA) pain.
Tanezumab is a humanized monoclonal antibody that selectively targets, binds to, and inhibits nerve growth factor. The investigational treatment is administered by subcutaneous injection every 8 weeks by a certified health care professional.
The joint FDA advisory committee reviewed data from 20 clinical studies, including three phase 3 studies that evaluated the efficacy and safety of tanezumab in patients with moderate to severe OA of the knee or hip. Findings from a trial comparing tanezumab to nonsteroidal anti-inflammatory drugs (NSAIDs) showed a statistically significant improvement in pain and physical function with tanezumab 5mg, however patient overall assessment of OA was not observed to be statistically different from NSAIDs. Additionally, the tanezumab 2.5mg group did not meet any of the 3 efficacy endpoints. As for safety, treatment with tanezumab was associated with a statistically significantly higher rate of joint safety events compared with NSAIDs at 80 weeks (7.1% for tanezumab 5mg, 3.8% for tanezumab 2.5mg, and 1.5% for NSAIDs).
In meeting documents, the panel members stated that while the clinical program for tanezumab did demonstrate its effectiveness, the effect size was “modest” and did not prove to be superior to NSAIDs. Moreover, the experts pointed out 2 serious toxicities associated with the investigational treatment: joint destruction (ie, rapidly progressing osteoarthritis [RPOA]), which may be increased with concomitant NSAID use, and neuropathy. Additional issues of concern included a potential elevated risk for total joint replacement in tanezumab-treated patients, as well as evidence indicating the drug may target healthy joints.
To ensure safe use, the Company proposed that tanezumab be marketed under a REMS that includes provider certification, patient enrollment, and extensive monitoring (bilateral X-rays of the knees and hips at baseline, then yearly; monitoring for pain of RPOA). “In spite of the risk mitigation strategies in clinical studies, the risk of developing RPOA remained concerning, as a large number of patients with RPOA required total joint replacements,” the panel members noted in the documents. “In addition, the required precision and consistency of the medical imaging and interpretation do not appear feasible in practice.”
Although not bound by the committees’ recommendations, the FDA does take them into consideration when making decisions on approval.
Commenting on the vote, Ken Verburg, tanezumab development team leader, Pfizer Global Product Development, said: “While we are disappointed with today’s outcome, we continue to believe that tanezumab has a positive benefit-risk profile for patients with moderate-to-severe osteoarthritis pain for whom current treatments are ineffective or not appropriate. We will continue to work with the FDA as the agency continues its review of our application.”
1. Joint FDA advisory committee votes on application for tanezumab for the treatment of osteoarthritis pain. [press release]. New York, NY, Indianapolis, IN: Eli Lilly; March 25, 2021.
2. FDA Briefing Document: Joint Meeting of the Arthritis Committee and Drug Safety and Risk Management Advisory Committee. https://www.fda.gov/media/146867/download. March 24-25, 2021.