Ab­b­Vie's stock and next megablock­buster take hits fol­low­ing new JAK warn­ings from FDA

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.”

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

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The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

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Vicente Anido (University of West Virginia via YouTube)

Aerie fires CEO af­ter lead pro­gram flop, com­ments about pri­ma­ry end­points be­ing 'not re­quired'

Aerie Pharmaceuticals CEO Vicente Anido has left the company less than a week after trying to chart a Phase III study in the wake of a serious Phase IIb flop.

Anido’s last day at Aerie was Friday, the biotech announced in a news release Tuesday morning, and Benjamin McGraw is taking his place in an interim role. The now former CEO was terminated without cause, according to an SEC filing.

The board has started looking for a full-time chief to take his place.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

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Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a specific market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

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Take­da snaps up the Japan­ese rights to an old Shire cast-off; Boehringer In­gel­heim ac­quires Abexxa Bi­o­log­ics

A week before the FDA is set to decide on Mirum Pharmaceuticals’ lead liver disease drug — an old Shire cast-off called maralixibat — Takeda is swooping in to secure the rights in Japan.

Maralixibat’s roots trace back to Lumena, which was snapped up by Shire for $260 million-plus back in 2014. While the candidate had failed mid-stage studies at Shire, Mirum believes better trial design and patient selection will deliver the wins it needs. The drug is currently in development for Alagille syndrome (a condition called ALGS in which bile builds up in the liver), progressive familial intrahepatic cholestasis (PFIC, which causes progressive liver disease) and biliary atresia (a blockage in the ducts that carry bile from the liver to the gallbladder).