Pfizer has run 41 trials over 15 years for tanezumab. As adcomm nears, the FDA remains unimpressed — and more than a little worried
Ahead of an advisory committee meeting later this week, the FDA on Monday released its in-depth review of Pfizer and Eli Lilly’s anti-NGF osteoarthritis drug tanezumab, concluding that it “provides substantial evidence of effectiveness” but also raising concerns that the proposed risk evaluation and mitigation strategy (REMS) may not be enough to lessen its significant safety risks.
The safety questions at hand deal with reports of unusual and unexpected joint-related adverse events in tanezumab-treated patients with osteoarthritis, FDA explained, noting, “The review team has concerns that the Applicant’s proposed REMS is not sufficient to mitigate the risk of RPOA [Rapidly Progressing Osteoarthritis] and would not ensure that the benefits of tanezumab outweigh the risks of RPOA.”
The FDA on Wednesday and Thursday (for a half day) will convene a joint meeting of its Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee to review the monoclonal antibody. The committees will vote on one question at the end of the meetings, “Will the REMS proposed by the Applicant ensure that the benefits of tanezumab outweigh its risks?”
Although FDA said tanezumab proved to be effective, its effect size “is modest, and there is no convincing evidence of a superior efficacy of tanezumab over NSAIDs.”
And the agency said there is “no clear evidence to support that requiring and implementing the proposed elements” of the REMS will have an impact on preventing or the progression of the joint-related risks.
“Most of the joint safety events were detected towards the end of the treatment and during the follow-up period after the cessation of treatment. As there is no evidence that the risk plateaus, it is unknown whether the rates and risk will accelerate or plateau with continued dosing past one year,” FDA said in its briefing document.
In addition, the agency said tanezumab is associated with an elevated risk of requiring a total joint replacement, as observed in two of the three post-2015 clinical studies, with evidence of dose response. There is also evidence that the risk for developing joint destruction is 2- to 3-fold higher if NSAIDs and tanezumab are used together, FDA said.
“Furthermore, even if the mitigation strategies employed in the clinical trial demonstrated effectiveness, it is unclear that those strategies could be replicated in clinical practice,” FDA said.
The adcomm meetings later this week will cap a long and question-filled development program for tanezumab, which has been in development for more than 15 years, across 41 clinical studies and at least 43 formal meetings with the FDA.