Series of JAK inhibitor delays may signal an upcoming FDA adcomm
Three-month review delays from the FDA have become the norm in recent days for JAK inhibitors, some of which are seeking label expansions.
But the pushback of these action dates for AbbVie’s Rinvoq, Pfizer’s Xeljanz and abrocitinib, and Eli Lilly’s Olumiant may be a sign that the FDA is preparing to hold an advisory committee of outside experts to review the risk/benefit profiles of JAK inhibitors for atopic dermatitis, according to SVB Leerink analyst Geoffrey Porges. This wouldn’t be the first time this year that the FDA wants to review a series of drugs before an adcomm as the agency is holding such a review later this month for cancer drugs that have previously won accelerated approvals.
“This is not a complete surprise given the FDA’s cautious stance on JAK inhibitors generally, their reluctance to approve the higher doses mostly required for efficacy in atopic dermatitis, and their recent actions on applications from all the JAK developers,” Porges writes. “While the FDA’s more stringent approach to JAKs as a drug class increases the perceived level of risk to the category’s outlook, we believe that ultimately Pfizer’s abrocitinib should get approved in this indication given its relatively clean profile (vs. Xeljanz).”
Any failures for these JAK inhibitors in atopic dermatitis will further firm up Regeneron and Sanofi’s top position with Dupixent, “given its excellent safety track record in this indication,” Porges writes.
He also says AbbVie indicated that FDA’s request for more information on Rinvoq was driven by Pfizer’s announcement in late January that Xeljanz failed a six-year safety study mandated by the FDA.
“While we do not expect any JAKs to be used ahead of Dupixent in AD, the strong results from the 30mg dose in the head-to-head study make Rinvoq a contender for second line treatment,” he adds. “Given the mixed history of JAKs and hesitancy from dermatologists to utilize JAKs in AD, an AdComm may be an effective platform to differentiate between JAK candidates in AD, which could benefit Rinvoq.”
Overall, Porges thinks the JAK inhibitor delays once again show an FDA that’s hardening its stance against the industry, particularly with respect to safety issues.
“There is a perception among investors that the FDA has become more active and demanding under new acting commissioner Janet Woodcock,” Porges adds in another investor note this week. “If this is a sea change (rather than a coincidence of timing), then it seems sensible to assume that regulatory applications with any uncertainties or questions have a higher-than-expected risk of being delayed and will be subject to further information requests and advisory committee reviews. This is consistent with most of the era of modern regulation of the biopharma industry, but not so much with the last 4-5 years.”