FDA Cites Safety Concerns Over Pfizer and Lilly’s Osteoarthritis Drug Tanezumab
A newly published briefing document from the U.S. Food and Drug Administration (FDA) cites critical safety concerns with Pfizer and Eli Lilly’s anti-NGF osteoarthritis drug tanezumab, despite the fact that clinical trials have demonstrated the agent can help patients with osteoarthritis.
The primary safety concern associated with the drug is rapidly progressing osteoarthritis (RPOA), which both Pfizer and Eli Lilly have observed in their research. The companies are currently looking to evaluate and monitor the drug and the associated safety issue under the FDA’s Risk Evaluation and Mitigation strategy (REMS).
But despite these good intentions, the agency said in the review document that the “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 FDA added that despite the clinical risk mitigation strategies put forth by the companies in the study, the risk of RPOA remains concerning as a substantial proportion of patients with this adverse event require total joint replacements. In particular, 15% of patients progressed to total joint replacement (TJR) after RPOA1, while 60% of patients progressed to TJR after RPOA2.
Also, the FDA further noted that drug cessation following the development of RPOA “does not appear to be effective in preventing further damage to the joints.”
Also, tanezumab may cause abnormal peripheral sensation, mostly characterized as mild and sometimes self-limited mononeuropathy.
According to the briefing document, the FDA has yet to make a final decision on the REMS application. The agency review team will further examine additional insights from the companies at an upcoming Advisory Committee meeting, the document reads.
Development of tanezumab spans over 15 years; the investigational new drug application was first submitted in April 2004. The drug was initially proposed as a painkiller for several different painful conditions in an effort to support approval for a broad pain indication. Pfizer has conducted a total of 41 clinical studies, 38 interventional trials and three observational studies, all surpassing nearly 18,000 participants.
Back in April 2019, Pfizer and Eli Lilly announced top-line results from a Phase III, 3,021-person trial featuring two doses of tanezumab in moderate-to-severe osteoarthritis of the knee or hip. The findings were mixed, as the 5 mg dose group met two of the three coprimary efficacy endpoints but missed on the overall assessment of osteoarthritis. Additionally, the 2.5 mg group did not experience a statistically significant improvement in their pain physical function or overall assessment.
There were also more safety events in the tanezumab arms compared with the groups of patients who received only non-steroidal anti-inflammatory drugs. A total of 10 deaths were reported in the study, nine of which were in the number cohort. The investigators sad that none of these deaths were believed to be related to study treatment.
Later in October 2020, Pfizer and Eli Lilly both announced that the drug resulted in consistent improvements in pain relief and physical function in several Phase III osteoarthritis trials. However, increasing doses of tanezumab in these trials led to a higher incidence of adverse events, including abnormal peripheral sensation.
“Adverse events of possible decreased sympathetic function were balanced across treatment groups, and there was no evidence of sympathetic nervous system dysfunction from tanezumab,” the researchers noted.