Pfizer and Eli Lilly announced top-line results showing that the high dose of the NGF inhibitor tanezumab met two of three co-primary efficacy endpoints in a Phase III study, with patients suffering from moderate-to-severe osteoarthritis (OA) of the hip or knee achieving significant improvement in pain and physical function compared to nonsteroidal anti-inflammatory drugs (NSAIDs) at the 16-week analysis, while patients' overall assessment of their OA did not differ significantly from NSAIDs. Meanwhile, the lower dose tested in the trial missed all three co-primary endpoints.
In addition, the companies reported nine deaths in the tanezumab treatment arms and one in the NSAID group, although "none were considered treatment-related." Specifically, five of the deaths occurred during the treatment period and five happened afterwards, they noted. Further, preliminary safety data showed that while the overall adverse event profile with tanezumab was "generally consistent" with previous studies of tanezumab in OA, discontinuations in this trial due to adverse events were higher among tanezumab-treated patients during the 56-week treatment period, the companies said.
"We are analysing these findings in the context of the recent Phase III results as we assess potential next steps for tanezumab," commented Ken Verburg, tanezumab development team leader at Pfizer's global product development. "We plan to review the totality of data from our clinical development programme for tanezumab with regulatory authorities," he added.
The A4091058 study randomised 3021 patients with moderate-to-severe OA to receive 2.5 mg or 5 mg of tanezumab administered subcutaneously every eight weeks, or oral NSAIDs twice daily, over a 56-week period. Patients were on a stable dose of NSAIDs before being screened into the study and had experienced at least some benefit from stable NSAID treatment. The study also included a 24-week safety follow-up period, for a total of 80 weeks of observation.
The main safety goals evaluated a composite measure of adjudicated outcomes of rapidly progressive osteoarthritis (RPOA) type 1 or type 2, subchondral insufficiency fracture, primary osteonecrosis or pathological fracture through 80 weeks. Findings from the safety analysis indicate there was a significantly higher rate of joint safety events in the tanezumab arms compared to NSAIDs at 80 weeks. Pfizer and Eli Lilly said the incidence of the primary composite joint safety endpoint was 7.1 percent and 3.8 percent in the 5-mg and 2.5-mg tanezumab arms, respectively, versus 1.5 percent in the NSAIDs arm. The rate of RPOA, which accounted for the majority of events observed, was 6.3 percent in the higher-dose tanezumab arm, 3.2 percent for the lower dose and 1.2 percent in the NSAID group.
Further, one patient in the 5-mg tanezumab arm had osteonecrosis, while there were no cases of osteonecrosis in the two other study groups. Subchondral insufficiency fracture was observed in seven, six and four patients receiving tanezumab 5 mg, tanezumab 2.5 mg and NSAIDs, respectively, and there were no cases of pathological fractures seen in any of the study participants. The companies said full results from the trial would be submitted for future publication or presentation.
Earlier this year, Pfizer and Eli Lilly reported findings from the Phase III A4091057 study testing tanezumab, at doses of either 2.5 mg or 5 mg, against placebo in certain patients with moderate-to-severe OA pain. Preliminary data from that trial indicated that the higher dose of tanezumab had met all three co-primary endpoints of pain and physical function, as well as patients' overall assessment of their OA. The lower dose also significantly improved pain and physical function versus placebo, but there was no difference in OA assessment.
In February, the companies reported positive late-stage results in patients with moderate-to-severe chronic low back pain.
Pfizer and Eli Lilly formed a partnership in 2013 to jointly develop and market tanezumab. The drug later received a fast-track designation by the FDA for the treatment of chronic pain associated with OA and chronic low back pain.
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