UPDATED: FDA Advisory Committee Raises Objections to Pfizer and Eli Lilly’s Tanezumab
Three days after U.S. Food and Drug Administration (FDA) staff raised safety concerns over Pfizer’s and Eli Lilly’s NGF osteoarthritis drug tanezumab, an advisory panel has also posted its own objections.
According to a breaking news report on Seeking Alpha, the FDA panel of experts recommended against approval of tanezumab in this indication. The panel overwhelmingly said the risks of taking the medication do not outweigh the therapeutic benefits. The committee voted 19-1 against approval of the drug application. The FDA is not bound to follow the recommendation of the committee but typically does.Pfizer said it will continue to work with the FDA as the agency reviews the application.
As BioSpace previously reported, the primary safety concern raised by the FDA staff concerned rapidly progressing osteoarthritis (RPOA), which both pharmaceuticals observed during their research. The two companies hoped to evaluate and monitor the drug and the associated safety issue under the FDA’s Risk Evaluation and Mitigation strategy (REMS). However, the FDA said in the review document that the “proposed REMS is not sufficient to mitigate the risk of RPOA and would not ensure that the benefits of tanezumab outweigh the risks of RPOA.”
Additionally, the staff said the risk of RPOA remains concerning as a substantial proportion of patients with this adverse event require total joint replacements. In particular, 15% of patients progressed to total joint replacement (TJR) after RPOA1, while 60% of patients progressed to TJR after RPOA2, BioSpace reported last week. The FDA also noted that drug cessation following the development of RPOA “does not appear to be effective in preventing further damage to the joints.” Additionally, tanezumab may cause abnormal peripheral sensation, mostly characterized as mild and sometimes self-limited mononeuropathy, the FDA said.
The advocacy group Public Citizen echoed the FDA staff and also discouraged the approval. Earlier this week the organization said the drug fails to provide meaningful relief of arthritis symptoms but does cause a dramatic increase in the rates of serious joint damage and of total joint replacements.
“A drug like tanezumab that accelerates the joint destruction of the underlying osteoarthritis disease it is intended to treat but lacks any evidence of clinically meaningful benefit in comparison to use of a placebo or oral NSAIDs obviously should never be approved by the FDA. It is baffling why the FDA felt it needed to bring the application for this drug before the advisory committees,” Public Citizen said in a statement.
Tanezumab, the medication used in the clinical trial, is a monoclonal antibody that is part of an investigational class of non-opioid pain medications known as nerve growth factor (NGF) inhibitors. By inhibiting NGF, tanezumab may help to keep pain signals produced by muscles, skin and organs from reaching the spinal cord and brain, the companies said.
In 2019, Pfizer and Eli Lilly announced mixed results from a Phase III study in moderate-to-severe osteoarthritis (OA) of the hip or knee. In addition to the mixed efficacy results from different dosing levels, the two companies reported more safety events in the tanezumab arms.
Eli Lilly’s Ilya Yuffa, president of Lilly Bio-Medicines, said the dialogue from the open public forum of this week’s Advisory Committee meeting reinforced the urgent need for innovation for people living with moderate-to-severe osteoarthritis pain. Yuffa said many of these patients tend to cycle through three or four different therapies without real relief.
“While we are disappointed with today’s outcome, we continue to believe that tanezumab has a positive benefit-risk profile for patients with moderate-to-severe osteoarthritis pain for whom current treatments are ineffective or not appropriate. Many of these patients have exhausted available therapies, have not had a new class of medications available to them in more than a decade and are eager for new, non-opioid options,” Ken Verburg, tanezumab development team leader at Pfizer Global Product Development said in a statement.