FDA Raises Significant Safety Concerns Over Pfizer and Lilly's Osteoarthritis Drug Tanezumab Despite Demonstrated Efficacy

Compiled by Keke

Although clinical trials have demonstrated that tanezumab, an anti-NGF osteoarthritis drug developed by Pfizer and Eli Lilly, can be used to treat patients with osteoarthritis, a recently released briefing document from the U.S. FDA still raises serious safety concerns regarding this drug.

The primary safety concern associated with this drug is the occurrence of rapidly progressive osteoarthritis (RPOA), which has been observed in studies conducted by both Pfizer and Eli Lilly. Both pharmaceutical companies are currently evaluating and monitoring tanezumab and its associated safety issues in accordance with the U.S. FDA’s Risk Evaluation and Mitigation Strategy (REMS).

But despite these good intentions, the U.S. FDA still stated in its review documents that “the proposed REMS is insufficient to mitigate the risk of RPOA occurrence and cannot ensure that the benefits of tanezumab outweigh the risks of RPOA.”

The U.S. FDA further noted, “Although the two companies proposed clinical risk mitigation strategies in their studies, concerns regarding RPOA remain, as a substantial proportion of patients experiencing adverse events required total joint replacement. Specifically, 15% of patients with RPOA1 and 60% of patients with RPOA2 progressed to requiring total joint replacement (TJR).”

Furthermore, the U.S. FDA further emphasized that “discontinuation of treatment after the development of RPOA ‘does not appear to effectively prevent further joint damage.’ Moreover, tanezumab can cause abnormal peripheral sensations, primarily manifesting as mild, and sometimes self-limiting, mononeuropathy.”

Reportedly, the development of tanezumab spanned 15 years, with its Investigational New Drug (IND) application first submitted in April 2004. The drug was initially proposed as an analgesic for several different pain conditions, aiming to support approval for indications covering a broad spectrum of pain. Pfizer conducted a total of 41 clinical studies, comprising 38 interventional trials and 3 observational studies, involving nearly 18,000 participants.

In April 2019, Pfizer and Eli Lilly announced the latest results from a Phase III clinical trial involving 3,021 patients with moderate-to-severe osteoarthritis of the knee or hip. The results were mixed: the tanezumab 5 mg dose group met two of the three primary efficacy endpoints but did not include an overall assessment of osteoarthritis. Meanwhile, the 2.5 mg dose group showed no statistically significant improvement in pain, physical function, or overall assessment.

Compared with the group of patients receiving only nonsteroidal anti-inflammatory drugs (NSAIDs), the tanezumab treatment group also experienced more safety events. The study report documented a total of 10 patient deaths; however, the researchers stated that these deaths were unrelated to the treatment.

Furthermore, evidence indicates that the concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and tanezumab increases the risk of joint destruction by 2- to 3-fold.

In October 2020, Pfizer and Eli Lilly announced that tanezumab demonstrated consistent efficacy in alleviating pain and improving physical function across several Phase III trials for osteoarthritis. However, in these trials, increasing the dose of tanezumab led to a higher incidence of adverse events, including abnormal peripheral sensation.

The researchers explained, “Adverse events involving potential declines in sympathetic function were balanced across treatment groups, with no evidence suggesting that tanezumab causes sympathetic nervous system dysfunction.”

According to the latest briefing document, the U.S. FDA has not yet made a final decision on the REMS applications submitted by Pfizer and Eli Lilly. The document states that its regulatory review team will further examine additional evidence and perspectives from the two pharmaceutical companies at an upcoming advisory committee meeting.

Reference Source: FDA Cites Safety Concerns Over Pfizer and Lilly’s Osteoarthritis Drug Tanezumab