Pfizer announced topline results from a long-term phase 3 study of tanezumab in patients with moderate to severe osteoarthritis (OA) of the hip or knee.
Study A4091058 was a double-blind, active-controlled, parallel-group study evaluating the safety and efficacy of tanezumab (administered subcutaneously) for 56 weeks compared with nonsteroidal anti-inflammatory drugs (NSAIDs); a 24-week safety follow-up period was also included. Patients (N=3021) were randomized to receive either tanezumab 2.5mg every 8 weeks, tanezumab 5mg every 8 weeks, or oral NSAIDs (either naproxen 500mg, celecoxib 100mg, or diclofenac extended-release 75mg) twice daily over the treatment period.
The co-primary efficacy endpoints were changes from baseline to week 16 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale, the WOMAC Physical Function subscale, and the Patient’s Global Assessment of OA. The primary safety endpoint was a composite measure of adjudicated outcomes of rapidly progressive osteoarthritis (RPOA) type 1 (defined as a significant loss of joint space width ≥2mm [predicated on optimal joint positioning] within approximately 1 year, without gross structural failure) or type 2 (defined as abnormal bone loss or destruction, including limited or total collapse of at least 1 subchondral surface that is not normally present in conventional end-stage OA), subchondral insufficiency fracture, primary osteonecrosis or pathological fracture through 80 weeks.
Results showed that at the 16-week analysis, tanezumab 5mg was associated with a statistically significant improvement in pain and physical function vs NSAIDs, however patient’s overall assessment of OA was not statistically different from NSAIDs; the tanezumab 2.5mg group did not meet any of the 3 efficacy endpoints. As for safety, treatment with tanezumab was associated with a statistically significantly higher rate of joint safety events (composite measure) compared with NSAIDs at 80 weeks (7.1% for tanezumab 5mg, 3.8% for tanezumab 2.5mg, and 1.5% for NSAIDs).
“We are analyzing these findings in the context of the recent phase 3 results as we assess potential next steps for tanezumab,” said Ken Verburg, tanezumab development team leader, Pfizer Global Product Development. “We plan to review the totality of data from our clinical development program for tanezumab with regulatory authorities.”
Tanezumab is a humanized monoclonal antibody that selectively targets, binds to, and inhibits nerve growth factor (NGF). In addition to OA, tanezumab is also being investigated for the treatment of chronic low back pain and cancer pain due to bone metastasis.