Pfizer and Eli Lilly’s long journey to a potential FDA approval for tanezumab still looked rocky today after review documents from the regulator cast doubt over its safety.
Ahead of an outside expert committee meeting midweek, the FDA as always released its thoughts and discussion points on the drug, and, while finding strong evidence that it helps osteoarthritis patients, it says there are critical safety risks that may cost the partners a straight shot on goal.
The main safety worry is so-called rapidly progressing osteoarthritis, or RPOA, which the companies are aware of. They are looking to run the drug under the FDA’s Risk Evaluation and Mitigation Strategy (REMS) to try to keep a close eye on this issue.
The FDA, however, is not convinced. “The review team has concerns that the Applicant’s proposed REMS is not sufficient to mitigate the risk of RPOA and would not ensure that the benefits of tanezumab outweigh the risks of RPOA,” the U.S. regulator said in the review documents.
“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 (TJR); 15% of patients progressed to total joint replacement (TJR) following RPOA1, and 60% of patients with RPOA2 progressed to TJR.”
It added that stopping drug after patients develop RPOA also “does not appear to be effective in preventing further damage to the joints,” while needing precision and consistency of the medical imaging and interpretation it says “do not appear feasible in practice.”
Another black mark was that the drug can cause abnormal peripheral sensation characterized as (predominantly) mild, self-limited mononeuropathy (singular nerve damage), with the most common coming out as carpal tunnel syndrome.
While saying that overall, the drug appears to work, it saw its efficacy as “modest” and not showing up better than much older and cheaper non-steroidal anti-inflammatory drugs (NSAIDs).
RELATED: Lilly, Pfizer's phase 3 pain data show mixed efficacy, clear safety issues
This is probably not altogether surprising: Two years back, Pfizer and Lilly published phase 3 data that painted a mixed picture of the safety and efficacy of the pair’s painkiller. Neither dose of the nerve growth factor inhibitor hit all the co-primary efficacy goals, and both fared worse than placebo on the safety assessments.
At the time, Wolfe Research analyst Tim Anderson did not mince his words: “To us, the product is likely dead, if not from a regulatory standpoint (i.e., is it even approvable?) then from a commercial one (i.e., will it ever sell?).”
The FDA documents conclude that: “No final decision has been made for this application, however, and the entire review team greatly looks forward to the insights that you can provide at the advisory committee meeting.” That happens Wednesday, but it might not be the easiest of days for the pharmas and comes after a 15-year journey for this tortured drug.