Regeneron halts high doses of phase 3 osteoarthritis drug fasinumab amid risk-benefit concerns

Competition in the field was intense around the start of the decade, only for the FDA top issue clinical holds. (Regeneron)

Regeneron has halted the higher-dose arms of its phase 3 fasinumab trials on the recommendation of a data monitoring committee. The committee made the call after assessing the risk-benefit profile of the osteoarthritis regimens based on data generated to date.

Tarrytown, New Jersey-based Regeneron is evaluating the anti-NGF antibody in patients with osteoarthritis of the knee or hip, plus chronic low back pain in some cases, across a suite of phase 3 trials. The most advanced of the studies have already enrolled thousands of patients. Some of the early findings paint certain doses of fasinumab in an unfavorable light.

Regeneron has been testing multiple regimens of fasinumab in the late-phase program but will now narrow its focus to the lower doses. The data monitoring committee signed off on the continuation of these lower-level regimens while expressing reservations about higher doses.


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Details of what the data monitoring committee found are yet to emerge but the risk fasinumab will exit phase 3 with a unfavorable risk-benefit profile is well established and acknowledged. Talking to investors in February, Regeneron CSO George Yancopoulos, Ph.D., described the fasinumab program as an “enormous opportunity balanced by a significant risk.”

The risk stems from problems encountered by the once-hyped class of anti-NGF antibodies in the past. Competition in the field was intense around the start of the decade, only for the FDA to hit drugs in development at Johnson & Johnson, Regeneron and Pfizer with clinical holds. The actions followed reports of joint replacements in clinical trial participants.

Exactly why arthritis accelerated in some patients who received the drugs is unclear. One theory is that the therapies effectively worked too well, causing the newly-pain-free people to use their joints more and therefore accelerate deterioration.

Whatever the cause, Regeneron thinks the dire need for non-opioid painkillers and the prevalence of patients with very severe osteoarthritis means its drug has a shot at having a positive overall profile, even if it is linked to deterioration in some people.

Regeneron is one of a small number of companies that held out hope for a positive profile as safety concerns mounted earlier in the decade. Pfizer is another. The Big Pharma is set to post phase 3 data on its Eli Lilly-partnered tanezumab this year.

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