While the FDA’s new warn­ings on JAK in­hibitors are based on a re­view of a Pfiz­er tri­al, it’s Ab­b­Vie that may be hurt the most.

Ab­b­Vie’s stock fell by about 10% at one point Wednes­day as its prized JAK in­hibitor Rin­voq, once fore­cast to haul in $8 bil­lion an­nu­al­ly by 2025, was looped in­to new class-wide FDA warn­ings, which in­clude risks of se­ri­ous heart-re­lat­ed events, can­cer, blood clots and death.

The re­view from the FDA fol­lows Pfiz­er’s an­nounce­ment in Jan­u­ary that its six-year post-mar­ket­ing tri­al for its JAK in­hibitor Xel­janz, known as ORAL Sur­veil­lance, had failed. Across 4,362 pa­tients, those who re­ceived ei­ther a low or high dose of Xel­janz ex­pe­ri­enced more ma­jor car­dio­vas­cu­lar events — such as stroke and heart at­tack — than those on com­para­tor TNF drugs Hu­mi­ra or En­brel. They al­so had high­er rates of can­cer with Pfiz­er fail­ing to hit non-in­fe­ri­or­i­ty on both pri­ma­ry end­points.

First ap­proved in 2019 for rheuma­toid arthri­tis, Rin­voq brought in $731 mil­lion in 2020 sales.

While Rin­voq has not been stud­ied in tri­als sim­i­lar to the large safe­ty clin­i­cal tri­al that the FDA re­viewed for Pfiz­er’s Xel­janz, the agency still said that be­cause they share the same mech­a­nisms of ac­tion the FDA con­sid­ers these drugs may have sim­i­lar risks as seen in the Xel­janz safe­ty tri­al. Wall Street an­a­lysts took is­sue with the ex­trap­o­la­tion, point­ing to what oth­er reg­u­la­tors have done.

Rin­voq is al­so still un­der FDA re­view in atopic der­mati­tis, pso­ri­at­ic arthri­tis and anky­los­ing spondyli­tis, and those de­ci­sions may be com­ing soon as the FDA post­poned all of its re­views of JAK sNDAs un­til this re­view of the Xel­janz tri­al fin­ished.

SVB Leerink an­a­lyst Ge­of­frey Porges wrote in a note to in­vestors Wednes­day:

In­ter­est­ing­ly, out­side the US, oth­er reg­u­la­tors have nei­ther im­posed these re­stric­tions, nor im­posed such oner­ous safe­ty lan­guage, nor have they treat­ed all the drugs in the class equal­ly with re­spect to safe­ty. In our dis­cus­sions with in­vestors the up­dat­ed safe­ty lan­guage seemed to be the most like­ly out­come, but we and most in­vestors had not an­tic­i­pat­ed the re­stric­tion to post-TNF pa­tients (even though that is how Rin­voq and oth­er JAKs are al­ready be­ing used in the US due to step-ed­it poli­cies and for­mu­la­ry re­stric­tions). The FDA’s state­ments do not of­fer any in­sight about whether the cur­rent re­views of the Rin­voq sNDAs for pso­ri­at­ic arthri­tis, anky­los­ing spondyli­tis, and atopic der­mati­tis will be af­fect­ed by this de­ci­sion, or whether Pfiz­er’s abroc­i­tinib can still be ap­proved in atopic der­mati­tis. We tend to be­lieve that the new in­di­ca­tions will be ap­proved, but with the caveats im­posed by to­day’s over­all reg­u­la­to­ry ac­tion but this is high­ly un­cer­tain.

Porges pre­vi­ous­ly es­ti­mat­ed that los­ing any one of these Rin­voq in­di­ca­tions could pose a $500 mil­lion to $1.5 bil­lion hit to the com­pa­ny’s long-term rev­enue ex­pec­ta­tions.

Ab­b­Vie did not re­spond to a re­quest for com­ment on the new FDA warn­ings.

Over­all, Porges said Rin­voq’s po­ten­tial “is al­most cer­tain­ly re­duced in the USA, by this la­bel­ing. How­ev­er, it still seems fea­si­ble that the prod­uct can get to the $3.5-4.5bn in US sales re­quired to sup­port the com­pa­ny’s long term guid­ance of $8bn in peak sales.”

The biggest is­sue with the FDA’s ac­tions to­day, Porges added, “is not the safe­ty dis­clo­sure, but in­stead the re­stric­tion to sec­ond-or lat­er-line treat­ment. Ab­b­Vie cer­tain­ly con­tem­plat­ed mov­ing Rin­voq in­to the first-line set­ting in RA, and al­so in new in­di­ca­tions such as PsA, AS, AD and even IBD. Those first-line in­di­ca­tions are now off the ta­ble, at least for the fore­see­able fu­ture.”

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, just two weeks after submitting a supplemental BLA. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Rare diseases often have more than just physical effects on patients — especially when it comes to chronic conditions. In the case of the rare slow-growing blood cancer chronic lymphocytic leukemia (CLL), AbbVie wanted to try to assess the mental and emotional toll on patients.

So it surveyed more than 300 CLL patients, caregivers and physicians. While each group differed in how they felt — caregivers overwhelmingly (81%) felt positive about their role, for instance — patients described a “roller coaster” of emotions traversing diagnosis to treatment to remission and even relapse for some.

Back in 2018, Swiss drugmaker Ferring Pharmaceuticals made a big bet on Minnesota-based Rebiotix, buying up the company for its experimental poop-based drug implant to treat an infection caused by C. difficile, a potentially dangerous bacteria, in a new way.

Four years later, Ferring’s fecal microbiota transplant, dubbed RBX2660 or Rebyota, will face the FDA’s adcomm of outside vaccine experts on Sept. 22, debating whether the agency should license the transplant as a treatment for adults following antibiotic treatment for recurrent C. difficile infection.