Pfizer/Lilly Discontinue Tanezumab, The Likely End For A Class Dogged By Safety
Executive Summary
The nerve growth factor inhibitor for osteoarthritis pain is one of the last still in development after safety largely sidetracked the class of drugs.
The 15-year development road for a once high-profile drug – Pfizer Inc. and Eli Lilly and Company's nerve growth factor inhibitor tanezumab – came to a quiet end. Lilly disclosed in its third quarter sales and earnings call on 26 October that the partners had discontinued development of tanezumab for osteoarthritis pain after receiving a complete response letter from the US Food and Drug Administration and a negative opinion by the European Medicine Agency's Committee for Medicinal Products for Human Use.
The news spells the likely end for the class of drugs, which has shown promise as a novel approach to treating pain but has also been associated with serious safety risks. Tanezumab is one of the last of the NGF inhibitors still in development after other rivals dropped out of the development space. Regeneron Pharmaceuticals, Inc. and Teva Pharmaceutical Industries Ltd. also have fasinumab, which has demonstrated efficacy in Phase III but the companies have not committed to filing. (Also see "Regeneron Pipeline Progresses On Several Fronts Despite COVID-19 Focus" - Scrip, 5 Aug, 2020.)
FDA or EMA approval of tanezumab would have been the more surprising outcome in this case. FDA's Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee voted overwhelmingly against the risk/benefit profile of tanezumab in March. (Also see "Pfizer/Lilly Had Big Ambitions For Tanezumab; Are They Finally Dashed?" - Scrip, 25 Mar, 2021.) But Pfizer and Lilly had never updated investors or the public on the final outcome of FDA's deliberations.
The companies' decision to go forward with a regulatory filing despite a questionable risk benefit profile was considered a surprise at the time as most investors had written off the commercial viability of the drug. But Pfizer and Lilly said they collaborated closely with FDA on the filing and pointed to the high unmet need for therapeutic alternatives in pain. (Also see "Surprise! Pfizer And Lilly File Tanezumab For Pain With FDA Despite Safety Questions " - Scrip, 28 Jan, 2020.)
The big safety concern with tanezumab has been progressive joint damage in patients in the osteoarthritis clinical trials – including some cases leading to joint replacement. The safety issues emerged more than a decade ago when the class of drugs was put on clinical hold in 2010. (Also see "J&J, Regeneron follow Pfizer in clinical holds for anti-NGFs" - Scrip, 30 Dec, 2010.) AstraZeneca PLC and Johnson & Johnson went on to discontinue development of their NGF inhibitors while Pfizer and Regeneron sought risk-sharing partnerships for their drugs and attempted to better characterize the safety profile by studying lower doses and avoiding concomitant use with non-steroidal anti-inflammatories.
Lilly paid Pfizer $200m in 2015 when the Phase III trials testing tanezumab resumed and helped front the R&D costs. (Also see "Pfizer/Lilly And J&J Are Readying NGF Inhibitors For Phase III" - Pink Sheet, 23 Mar, 2015.) Teva paid $250m upfront to partner with Regeneron on fasinumab in 2016 and jointly share the R&D costs. (Also see "Regeneron Partners NGF Antibody With Teva To Mitigate Risks" - Scrip, 20 Sep, 2016.)
FDA's advisory committee did not think the safety precautions were sufficient, however. They said long-term safety data was needed as well as data on the prognosis of osteoarthritis patients who suffer joint damage and discontinue the treatment was still needed. And, the panel rejected Pfizer/Lilly's proposed risk management plan, which included certification requirements for prescribers, baseline and annual bilateral x-rays to monitor for joint damage and discontinuation of treatment in patients without a satisfactory clinical response after two doses. (Also see "Pfizer’s Tanezumab REMS Cannot Make Benefit-Risk Positive, US FDA Panel Says" - Pink Sheet, 25 Mar, 2021.)
Lilly's third quarter update did not focus on tanezumab as developments in Alzheimer's and other therapeutic areas continues dominated the call.