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.”

89bio said its drug was better than placebo at lessening fibrosis without worsening nonalcoholic steatohepatitis, or NASH, in two of three dose groups.

The San Francisco biotech said it thinks the Phase IIb data pave the way for a potential Phase III, following in the footsteps of another biotech in its drug class, Akero Therapeutics. To fund a late-stage study, CEO Rohan Palekar told Endpoints News 89bio “would need to raise additional capital,” with the company having about $188 million at the end of last year.

The National Institutes of Health has again declined to use so-called “march-in” rights to lower the price of Astellas and Pfizer’s prostate cancer drug Xtandi despite being invented at UCLA with grants from the US Army and NIH.

“Given the remaining patent life and the lengthy administrative process involved for a march-in proceeding, NIH does not believe that use of the march-in authority would be an effective means of lowering the price of the drug,” NIH told prostate cancer patients Robert Sachs and Clare Love, in a letter shared with Endpoints News. The institutes’ analyses found Xtandi “to be widely available to the public,” an indication that there was not a pressing need for the US to act.