FDA push­es eczema de­ci­sion for Eli Lil­ly's Olu­mi­ant, Pfiz­er's abroc­i­tinib back 3 months — rais­ing more ques­tions for the JAK class

The FDA re­view ex­ten­sions for JAK in­hibitors are stack­ing up.

Af­ter Eli Lil­ly and In­cyte dis­closed late Tues­day that their sup­ple­men­tal NDA for Olu­mi­ant in mod­er­ate to se­vere atopic der­mati­tis was hit with a 3-month de­lay, Pfiz­er re­vealed ear­ly Wednes­day that its ex­per­i­men­tal abroc­i­tinib is meet­ing the same fate. With Olu­mi­ant, the agency need­ed time to “re­view ad­di­tion­al da­ta analy­ses sub­mit­ted by Lil­ly in re­sponse to re­cent in­for­ma­tion re­quests from the FDA,” ac­cord­ing to a state­ment. Pfiz­er didn’t spec­i­fy a rea­son in its re­lease.

In ad­di­tion, the agency is al­so knock­ing back by 3 months a re­view of Pfiz­er’s Xel­janz for the treat­ment ac­tive anky­los­ing spondyli­tis.

The set­back puts Lil­ly and Pfiz­er in the same boat as Ab­b­Vie, which re­vealed days ago that reg­u­la­tors asked for an up­dat­ed ben­e­fit-risk pro­file of its JAK in­hibitor Rin­voq, push­ing their PDU­FA date to Q3 of 2021.

Safe­ty con­cerns with JAK in­hibitors are not new. In fact, fol­low­ing a rocky de­vel­op­ment path that in­volved an ini­tial re­jec­tion and re­stric­tions in dos­ing, Olu­mi­ant’s ini­tial ap­proval in rheuma­toid arthri­tis came with black box warn­ings on height­ened risks for se­ri­ous in­fec­tions, ma­lig­nan­cy and throm­bo­sis. Rin­voq sports a sim­i­lar la­bel.

The is­sues came to the fore again ear­li­er this year, when Pfiz­er an­nounced that its drug, Xel­janz, has failed the six-year safe­ty study man­dat­ed by the FDA.

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 Hu­mi­ra or En­brel. They al­so had high­er rates of can­cer, with Pfiz­er fail­ing to hit non-in­fe­ri­or­i­ty on both pri­ma­ry end­points.

Ilya Yuf­fa

Ilya Yuf­fa, pres­i­dent of Lil­ly Bio-Med­i­cines, says they stand by the ef­fi­ca­cy of Olu­mi­ant. The drug had scored wins in mul­ti­ple late-stage stud­ies in atopic der­mati­tis, beat­ing cor­ti­cos­teroids and place­bo in clear­ing eczema.

More re­cent­ly, it’s al­so gained promi­nence as the FDA grant­ed emer­gency use au­tho­riza­tion to a com­bi­na­tion of Olu­mi­ant and Vek­lury (remde­sivir) for hos­pi­tal­ized Covid-19 pa­tients who need sup­ple­men­tal oxy­gen, ven­ti­la­tors or life sup­port.

But its uti­liza­tion in atopic der­mati­tis has al­ways been ques­tioned. SVB Leerink an­a­lyst An­drew Berens pre­vi­ous­ly pre­dict­ed that it will play a “mi­nor role” in the dis­ease:

Giv­en the dom­i­nance of (Re­gen­eron’s) Dupix­ent in the mod­er­ate and se­vere AD mar­ket and known safe­ty risks of in­fec­tions, ma­lig­nan­cies, and throm­bo­sis with oral JAK in­hibitors, we be­lieve oral, sys­temic JAK in­hibitors may not cap­ture a mean­ing­ful por­tion of the AD mar­ket. While this pro­file rep­re­sents lim­i­ta­tions of the JAK class for sys­temic ther­a­py, we be­lieve this could open the door for a greater role for top­i­cal JAK us­age, which could be pre­scribed in con­junc­tion with non-JAK sys­temic treat­ment.

In­cyte, which had ini­tial­ly come up with the drug and al­lied with Lil­ly in ex­change for $90 mil­lion up­front back in 2009, has pulled out of co-fund­ing the de­vel­op­ment but con­tin­ues to be el­i­gi­ble for roy­al­ties on sales.

No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

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Demis Hassabis, DeepMind CEO (Qianlong/Imaginechina via AP Images)

Google's Deep­Mind opens its pro­tein data­base to sci­ence — po­ten­tial­ly crack­ing drug R&D wide open

Nearly a year ago, Google’s AI outfit DeepMind announced they had cracked one of the oldest problems in biology: predicting a protein’s structure from its sequence alone. Now they’ve turned that software on nearly every human protein and hundreds of thousands of additional proteins from organisms important to medical research, such as fruit flies, mice and malaria parasite.

The new database of roughly 350,000 protein sequences and structures represents a potentially monumental achievement for the life sciences, one that could hasten new biological insights and the development of new drugs. DeepMind said it will be free and accessible to all researchers and companies.

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In­side Bio­gen's scram­ble to sell Aduhelm: Pro­ject 'Javelin' and pres­sure to ID as many pa­tients as pos­si­ble

In anticipation of Aduhelm’s approval for Alzheimer’s in June, Biogen employees were directed to identify and guarantee treatment centers would administer the drug through a program called “Javelin,” a senior Biogen employee told Endpoints News.

The program identified about 800 centers for use, he said, and Biogen now pays for the use of bioassays to identify beta amyloid in potential patients having undergone a lumbar puncture procedure, the employee said — and one center preparing to administer the drug confirmed its participation in the bioassay program.

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EMA re­jects FDA-ap­proved Parkin­son's drug, signs off on Mod­er­na vac­cine use in ado­les­cents ahead of FDA

The European Medicines Agency on Friday rejected Kyowa Kirin’s Parkinson’s disease drug Nouryant (istradefylline), which the US FDA approved in 2019 under the brand name Nourianz.

EMA said it considered that the results of the clinical studies used to support the application “were inconsistent and did not satisfactorily show that Nouryant was effective at reducing the ‘off’ time. Only four out of the eight studies showed a reduction in ‘off’ time, and the effect did not increase with an increased dose of Nouryant.”

6 top drug­mak­ers of­fer per­spec­tives on FDA's new co­vari­ates in RCTs guid­ance

Back in May, the FDA revised and expanded a 2019 draft guidance that spells out how to adjust for covariates in the statistical analysis of randomized controlled trials.

Building on the ICH’s E9 guideline on the statistical principles for clinical trials, the 3-page draft was transformed into an 8-page draft, with more detailed recommendations on linear and nonlinear models to analyze the efficacy endpoints in RCTs.

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Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

No­var­tis dis­cards one of its ‘wild card’ drugs af­ter it flops in key study. But it takes one more for the hand

Always remember just how risky it is to gamble big on small studies.

A little more than 4 years ago, Novartis reportedly put up a package worth up to $1 billion for the dry eye drug ECF843 after a small biotech called Lubris put it through its paces in a tiny study of 40 moderate to severe patients, tracking some statistically significant markers of efficacy.

By last fall, the program had risen up to become one of CEO Vas Narasimhan’s top “wild card” programs in line for a potential breakthrough year in 2021. These drugs were all considered high-risk, high-reward efforts. And in this case, risk won.

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No­var­tis to pay near­ly $178M in law­suit over BRAF drug — and will be on the hook for roy­al­ty

After a four-year battle over a cancer drug patent, Novartis has been ordered by a California judge to pay a Daiichi Sankyo subsidiary $177.8 million.

Plexxikon filed a lawsuit against the pharma giant in 2017, alledging that Tafinlar, a rival to its melanoma drug Zelboraf that was brought to market in collaboration with Roche, has stepped on its intellectual property. The jury ruled in its favor, adding that the infringement is in fact willful.

Al Sandrock, Biogen R&D chief (Biogen via YouTube)

Bio­gen has a shaky end to H1 with a $542M write-off adding to its woes — but an­a­lysts see big rev­enue ahead for Aduhelm

All eyes at Biogen’s Q2 earnings call Thursday were on Aduhelm, but investors also got a glimpse of what Biogen would have faced had the FDA not opted to approve their controversial Alzheimer’s drug.

That glimpse, revealing a combination of declining sales, growing competition and failed medicines, underscores the stakes of the big biotech’s Aduhelm efforts, as execs punch back at the criticism they’ve engendered in the political and medical world and vigorously pushes its sales staff to roll out the drug as fast as possible.

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Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Valeriano Di Domenico)

Bio­gen de­fends slow roll­out of new Alzheimer's drug, crit­i­cizes neg­a­tive me­dia at­ten­tion

As Biogen execs bemoaned the negative media coverage around Aduhelm’s approval a month ago, the biotech isn’t gaining much traction yet in using its new drug, largely due to a lack of insurance coverage, according to an earnings call Thursday.

Management indicated that of the nearly 900 sites that were prepped and ready following Aduhelm’s approval, 325 of those, or about 35%, have completed a positive pharmacy and therapeutics (P&T) review or won’t require one. The review is a step some hospitals or health systems take prior to using a new drug. Some major sites, however, have said they won’t participate.