The FDA recently sent out two head-scratching notices to FibroGen and Acadia Pharmaceuticals, delaying decisions on their drug applications. Is it a sign of more challenging drug reviews to come? SVB Leerink analyst Geoffrey Porges warned investors that may be the case.
The FDA issued last-minute notices to FibroGen and its partner AstraZeneca on their anemia candidate roxadustat, and to Acadia for a label expansion on its neurology drug Nuplazid, raising surprising new hurdles they'll have to clear to win approvals.
Those two delays alone would not be enough to declare that the FDA is suddenly tightening its review process, Porges wrote in an investor note Tuesday, but then the FDA delayed its decision on label expansions for AbbVie’s immunology drug Rinvoq. That gives the theory of a more critical FDA significantly more weight, Porges said.
The delays, with the backdrop of a new President in the White House, “raise questions about whether the FDA under acting commissioner Janet Woodcock, who is effectively auditioning for the permanent role, is adopting a more stringent approach to drug reviews, at least for the time being,” Porges wrote. The Rinvoq decision indicates a "tougher posture from the FDA under the new administration,” he said in another note Wednesday,
The trouble started earlier this month with an announcement from FibroGen and AZ explaining that the FDA had told them it will convene an advisory committee to review roxa for treating anemia caused by chronic kidney disease.
An AdCom discussion, especially for a first-in-class drug-like roxa, isn't entirely surprising. But industry watchers and investors were shocked because the FDA told the companies three times that it wouldn’t hold such a meeting. What's more, the sudden change of stance came just three weeks before the scheduled decision date, which had already been pushed back by three months because of the FDA's request for more analysis of existing data.
As for Nuplazid, Acadia was aiming to expand the drug into dementia-related psychosis with a PDUFA data set for April 3. But on March 3, the FDA instead notified the company that it had identified deficiencies in the application that would preclude planned discussions about labeling and post-marketing requirements.
By Acadia’s account, it and the FDA has already agreed that one pivotal clinical program and supporting phase 2 data would suffice for the label expansion, and the company has responded to two data-related questions. Everything was still on track for the March 3 discussion, at least when Acadia reached out to the FDA on Feb. 18. And now, despite repeated attempts to obtain clarifications about the “deficiencies,” the FDA has been silent, the company said last week.
The Rinvoq setback extended the target action date for the drug’s application in psoriatic arthritis by three months to late second quarter. It came after the FDA requested an updated assessment of the benefit-risk profile for the JAK inhibitor in that indication. The FDA also raised questions related to a separate pending evaluation in atopic dermatitis. So the agency is now asking for more time to review the applications.
Porges suspects the FDA might have some concerns about how Rinvoq's higher, 30-mg dose, compares to the 15-mg dose of the drug that's approved in rheumatoid arthritis. Recently, the higher dose of another drug in the same JAK class, Pfizer's Xeljanz, was linked to an increased risk of serious heart-related problems and cancer.
“This is another example of what is clearly a new regulatory approach from the FDA—every potentially questionable or uncertain approval event seems to be pushed out, or re-evaluated, whereas investors may have had a high degree of confidence in their approval in the prior administration,” Porges said of the Rinvoq program in a Wednesday note.
A more restrictive FDA increases the risk to the biopharma industry, he said, warning investors that they should brace themselves for more such announcements. Now, drug programs with any “hair” on the phase 3 trial design or result could face review delays, AdComs, labeling restricting or outright rejections, he said.