Pfizer and Eli Lilly and Co. shared the results of a Phase III clinical trial evaluating the efficacy tanezumab in the treatment of moderate-to-severe osteoarthritis (OA) of the hip and knee compared to nonsteroidal anti-inflammatory drugs (NSAIDs). They found that low-dose tanezumab was not effective, while a higher dose of the drug only met some of the study’s primary endpoints.
“We are analyzing these findings in the context of the recent Phase III results as we assess potential next steps for tanezumab,” stated 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, a non-opioid painkiller, is part of a new group of medications that target the nerve growth factor. In the latest trial, a total of 3,021 patients were randomized to receive oral NSAIDs (naproxen 500 mg, celecoxib 100 mg, or diclofenac 75 mg), tanezumab 2.5 mg, or tanezumab 5 mg. The three primary endpoints were changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score, WOMAC physical function subscale score, and patient’s global assessment of OA.
Phase 3 study tanezumab (anti-NGF) 2.5 mg or 5 mgin knee or hip OA find that 5 mg met 2/3 of 3 primary endpoints at 16wks; but the lower dose failed to be superior to NSAIDs in this 1 yr study. Safety outcomes where less favorable w/ tanezumab. https://t.co/l4Qffdn1nl
— Dr. John Cush (@RheumNow) April 19, 2019
Tanezumab: Different Doses Yield Different Results
At 16 weeks, patients in the 5 mg tanezumab group showed significant improvement in pain and physical function compared to the NSAID cohort; however, global OA assessment did not differ between the groups. Meanwhile, patients in the low-dose tanezumab group did not achieve significantly different results compared to the NSAID group.
The study also evaluated safety outcomes and found that joint safety events occurred at a higher rate in both tanezumab cohorts compared to NSAID patients. Joint safety included rapidly progressive osteoarthritis (RPOA) type 1 or type 2, subchondral insufficiency fracture, osteonecrosis, and pathological fracture. Overall, joint safety incidence was 7.1% in the high-dose tanezumab group, 3.8% in the low-dose tanezumab group, and 1.5% in the NSAID group. The most common joint safety event was RPOA, which occurred at rates of 6.3%, 3.2%, and 1.2% in the high-dose tanezumab group, low-dose tanezumab group, and NSAID group, respectively; 81% of RPOA events seen in the tanezumab patients were RPOA type 1. There was one case of osteonecrosis, which occurred in the high-dose tanezumab group. Subchondral insufficiency fracture occurred in seven high-dose tanezumab patients, six low-dose tanezumab patients, and four NSAID patients. Total joint replacement rates were 8%, 5.3%, and 2.6% in the tanezumab 5 mg, tanezumab 2.5 mg, and NSAID groups, respectively. No pathological fractures occurred.
— Rheumatology Advisor (@RheumAdvisor) April 22, 2019
“Lilly and Pfizer recognize the significant unmet needs for patients living with osteoarthritis,” said Christi Shaw, president, Lilly Bio-Medicines. “We are committed to understanding these results for people who suffer from chronic pain.”
— Mazenz.com (@MazenzCom) April 18, 2019
Late-stage tanezumab data raises safety questions all over again for the drug class, putting pressure on a competitor to show a clean side effect profile https://t.co/wAQcoZKgMd
— BioPharma Dive (@BioPharmaDive) April 22, 2019