Drug Development, Setbacks

Safety threat forces FDA to put a hold on Regeneron, Teva’s big NGF pain drug fasinumab

George Yancopoulos

George Yancopoulos, Regeneron

Just one month after Teva agreed to pay Regeneron $250 million in cash to partner on its NGF pain program, the FDA has slapped a clinical hold on their Phase IIb study of fasinumab for lower back pain.

The hold was triggered after a patient in the study suffering from advanced osteoarthritis developed a case of adjudicated arthropathy – joint disease. And the new partners are countering the hold by planning to exclude osteoarthritis patients from a planned Phase III.

The deal between the two companies, which also included $2.3 billion in milestones, was the latest in a series of advancements in the late-stage field. And the hold raises old fears that these drugs could destroy patients’ joints.

NGF drugs were all the rage until five years ago, when some of the patients in clinical studies began to blow out their joints with meds designed to silence nerve growth factors. The safety issues sidelined the drugs, once tapped as likely blockbusters, but developers slowly worked out a plan to protect patients, and Pfizer got back into the clinic, with Eli Lilly signing on to partner in a $1.8 billion deal. J&J came back in right alongside, with falranumab, in-licensed from Amgen.

Even though J&J had a huge Phase III effort underway, with four late-stage studies, the pharma giant decided to abandon the work earlier this year, saying only that it was reprioritizing its pipeline.

Investigators on the fasinumab program say that as a result of the FDA decision they completed an unplanned interim review of the data that showed “clear evidence of efficacy.” But at least one analyst says that the setback may spur second thoughts at Teva, which is still on the hook for paying half of a billion-dollar Phase III program.

“Teva has paid $250M upfront to REGN, but the more serious cash outlays are yet to happen (i.e., Ph 3 outcomes),” notes Umer Raffat at Evercore ISI.  “This may be a good time to cut the losses – especially with this new update on clinical hold (does it trigger some “MAC” clause?).”

And Geoffrey Porges at Leerink was withering in his assessment of the drug, which he is now writing off as a complete loss:

Based on this hold, and the history of the class, we are reducing our probability of success to zero, and removing all fasinumab revenue (and future milestones) from our model and REGN valuation. The hold is for the low back pain program (phase IIb) but also involves additional scrutiny and changes to the development plans for the osteoarthritis program as well. We believe that these disclosures suggest that fasinumab will have all of the liabilities of prior drugs in this class, and will face the same repeated delays, increased scrutiny and labelling limitations that plagued other programs in the same class.

The NGF target has remained a tempting field in pain R&D, especially as fresh alarms over the epidemic of opioid addiction raises fears from coast-to-coast in the US. Finding a new way to treat pain without opioids would open up a big market, as regulators look for alternatives that can replace addictive treatments. And the Regeneron/Teva team are committed to making their drug work.

“We are making data-driven decisions on Phase 3 fasinumab dosing that we believe will maximize potential benefit for patients in need, while minimizing the likelihood of side effects,” said George D. Yancopoulos, Regeneron’s high profile CSO, in a statement. “We look forward to working with global health authorities to advance this important investigational therapy for patients with often difficult-to-treat osteoarthritis pain and chronic low back pain.”

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Sr. Manager, Regulatory Affairs, CMC
CytomX Therapeutics San Francisco, CA
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Catalytic Data Science Charleston, SC
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Flatiron Health New York City or San Francisco

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