The FDA is evaluating tanezumab, a non-opioid pain medication developed by Pfizer and Eli Lilly, as a potential treatment for chronic pain associated with moderate-to-severe osteoarthritis (OA). This marks a significant step for the drug, which belongs to the nerve growth factor (NGF) inhibitor class.
The FDA's standard 10-month review will determine if tanezumab can offer sufficient pain relief to OA patients who have not found adequate relief from other analgesics. A decision is expected in December. Tanezumab represents one of the last remaining drugs in the NGF inhibitor class, which once held promise as a non-addictive alternative to opioid painkillers.
Unmet Needs in Osteoarthritis Treatment
Pfizer estimates that approximately 27 million Americans suffer from osteoarthritis, with 11 million experiencing moderate to severe disease. Of these, a significant 80% have tried and failed to find relief with three or more analgesic medications, highlighting the urgent need for new treatment options.
The marketing application for tanezumab includes data from 39 Phase 1 to 3 trials involving approximately 18,000 subjects. The application seeks approval for a 2.5 mg subcutaneous dose. While this dose showed mixed results in previous osteoarthritis studies, a higher 5 mg dose was associated with a greater risk of rapidly progressing osteoarthritis.
Safety Concerns and Clinical Data
NGF inhibitors have been associated with a risk of rapidly progressing joint destruction, a safety concern that has led to the discontinuation of other drugs in the class. In a Phase 3 trial, rapidly progressive osteoarthritis was observed in less than 1.5% of tanezumab-treated patients, and not observed in the placebo arm. No events of osteonecrosis were observed in the trial, and no new safety signals were identified.
The trial enrolled 698 patients who were randomly selected to join three treatment groups. One group received two doses of placebo, the second received two doses of tanezumab 2.5mg, and the third group received a dose of tanezumab 2.5mg followed by a dose of tanezumab 5mg eight weeks later. Efficacy was measured using a standard assessment of knee arthritis pain and physical function, and the patient’s global assessment of osteoarthritis. Both treatment arms met all three of these goals.
Future Outlook
Given the safety concerns, the FDA has indicated it will convene an advisory committee meeting to discuss tanezumab's marketing application. Regeneron and Teva are also developing an anti-NGF antibody, fasinumab, for osteoarthritis pain. However, they halted higher dose arms of their Phase 3 trials due to concerns about the risk-benefit profile.
