Pfiz­er, still chas­ing Dupix­ent, re­leas­es fifth round of da­ta for eczema JAK in­hibitor abroc­i­tinib

Over the last sev­er­al months, Pfiz­er has been putting to­geth­er a pro­file of sev­er­al Phase III tri­als for its ex­per­i­men­tal JAK1 in­hibitor abroc­i­tinib to take to reg­u­la­tors, in the hopes of tak­ing down Dupix­ent. And on Wednes­day, the big phar­ma re­leased an­oth­er set of pos­i­tive topline da­ta.

In what’s now the fifth Phase III to re­port abroc­i­tinib da­ta, Pfiz­er said few­er pa­tients with atopic der­mati­tis ex­pe­ri­enced a flare up af­ter 52 weeks at mul­ti­ple dosage lev­els over place­bo. The study, which en­rolled 1,233 pa­tients 12 and old­er, in­volved a 12-week in­duc­tion fol­lowed by a 40-week blind­ed main­te­nance pe­ri­od.

Pfiz­er divvied up pa­tients even­ly in­to three arms — a 200 mg dose lev­el, a 100 mg arm and the place­bo group. Af­ter see­ing a re­sponse in the 200 mg in­duc­tion pe­ri­od, pa­tients who con­tin­ued in­to the treat­ment arms were sig­nif­i­cant­ly less like­ly to see their AD flare.

The prob­a­bil­i­ty for not flar­ing up in the high­est dose hit 81.1% and the 100 mg saw a 57.4% like­li­hood, while those in the con­trol group came in at 19.1%. Pfiz­er al­so said that these re­sults show pa­tients on the high­er dose were sig­nif­i­cant­ly less like­ly to flare than those on the low­er dose. The p-val­ues for both of these prob­a­bil­i­ties were less than 0.0001.

Ad­di­tion­al­ly, Pfiz­er said the re­spon­der rate in this tri­al af­ter the first 12 weeks was high­er than ex­pect­ed when com­pared to the pre­vi­ous abroc­i­tinib stud­ies. 798 out of the 1,233 pa­tients, or 64.7%, saw a re­sponse.

On safe­ty, al­ways a ques­tion with JAK in­hibitors, Pfiz­er saw no new safe­ty sig­nals in the tri­al. Dur­ing the main­te­nance pe­ri­od, the per­cent­age of pa­tients who ex­pe­ri­enced se­ri­ous side ef­fects were 4.9% and 1.5% in the drug arms and 0.7% in place­bo. More pa­tients treat­ed with abroc­i­tinib al­so dis­con­tin­ued from the study due to ad­verse events — 6%, 1.9%, and 1.5% in the re­spec­tive groups.

The NJ-based phar­ma is look­ing to catch Re­gen­eron and Sanofi’s block­buster Dupix­ent drug, which net­ted more than $1.9 bil­lion in sales through the first half of 2020. Pfiz­er has a few things go­ing in their fa­vor as Dupix­ent, an IL-4/IL-13 in­hibitor, is ad­min­is­tered sub­cu­ta­neous­ly where­as abroc­i­tinib is giv­en oral­ly.

But JAK in­hibitors like abroc­i­tinib have long faced scruti­ny in the safe­ty are­na, hand­i­cap­ping drugs some­times thought to have high sales po­ten­tial. Ab­b­Vie’s Rin­voq, for ex­am­ple, got a black box warn­ing af­ter stud­ies showed 1% of pa­tients got a se­ri­ous in­fec­tion, op­por­tunis­tic in­fec­tion, or her­pes zoster.

There have al­so been con­cerns about platelet re­duc­tion in abroc­i­tinib, as pre­vi­ous stud­ies have shown platelet counts drop­ping 26% for the 200 mg dose and 19% for the 100 mg group com­pared to es­sen­tial­ly no re­duc­tion on place­bo, though they even­tu­al­ly re­turned to nor­mal. And one an­a­lyst said in June that the da­ta re­leased up to that point would not make Pfiz­er’s can­di­date safe enough to be a “for­mi­da­ble” com­peti­tor to Re­gen­eron and Sanofi.

That re­port was fol­lowed by SVB Leerink’s Ge­of­frey Porges say­ing in Ju­ly that “near­ly all in­di­ca­tions” sug­gest Pfiz­er’s can­di­dates could be beat­en to mar­ket, or by bet­ter clin­i­cal da­ta, by oth­er oral­ly ad­min­is­tered JAK chal­lengers. Porges not­ed that in ad­di­tion to Rin­voq, black box warn­ings were slapped across the en­tire JAK class and had pre­vi­ous­ly stunt­ed Xel­janz sales. Ul­ti­mate­ly, Porges pre­dict­ed that abroc­i­tinib would end up rel­e­gat­ed to sec­ond-line treat­ment in eczema be­hind Dupix­ent.

By block­ing the Janus ki­nase, abroc­i­tinib is thought to mod­u­late mul­ti­ple cy­tokines in­clud­ing IL-4, IL-13, IL-31, IL-22 and in­ter­fer­on gam­ma. Dupix­ent, how­ev­er, in­hibits IL-4 and IL-13 di­rect­ly.

Biogen CEO Michel Vounatsos (via Getty Images)

With ad­u­canum­ab caught on a cliff, Bio­gen’s Michel Vounatsos bets bil­lions on an­oth­er high-risk neu­ro play

With its FDA pitch on the Alzheimer’s drug aducanumab hanging perilously close to disaster, Biogen is rolling the dice on a $3.1 billion deal that brings in commercial rights to one of the other spotlight neuro drugs in late-stage development — after it already failed its first Phase III.

The big biotech has turned to Sage Therapeutics for its latest deal, close to a year after the crushing failure of Sage-217, now dubbed zuranolone, in the MOUNTAIN study.

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As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

Af­ter Ko­dak de­ba­cle, US lends $1.1B to a syn­thet­ic bi­ol­o­gy com­pa­ny and their big Covid-19, mR­NA plans

In mid-August, as Kodak’s $765 million government-backed push into drug manufacturing slowly fell apart in national headlines, Ginkgo Bioworks CEO Jason Kelly got a message from his company’s government liaison: HHS wanted to know if they, too, might want a loan.

The government’s decision to lend Kodak three quarters of a billion dollars raised eyebrows because Kodak had never made drugs before. But Ginkgo, while not a manufacturing company, had spent the last decade refining new ways to produce materials inside cells and building automated facilities across Boston.

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Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

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Vivek Ramaswamy (Jeff Rumans/JPM 2020)

Urovan­t's lead drug dis­ap­points in mid-stage study as first big FDA de­ci­sion looms

Just as Urovant gets ready for its first big FDA decision on vibegron, the drug has flopped in what would’ve been a follow-on indication.

In a Phase IIa trial involving women with abdominal pain due to irritable bowel syndrome, vibegron failed to meet the bar on improving “average worst abdominal pain” over 12 weeks, compared to placebo, among IBS-D patients.

There were actually slightly more responders in the placebo group than in the drug arm, with only 40.9% of those randomized to vigebron achieving at least a 30% decrease in “worst abdominal pain” in the past 24 hours. The trial enrolled 222 women but only 189 completed the study.

Gen­mab ax­es an ADC de­vel­op­ment pro­gram af­ter the da­ta fail to im­press

Genmab $GMAB has opted to ax one of its antibody-drug conjugates after watching it flop in the clinic.

The Danish biotech reported Tuesday that it decided to kill their program for enapotamab vedotin after the data gathered from expansion cohorts failed to measure up. According to the company:

While enapotamab vedotin has shown some evidence of clinical activity, this was not optimized by different dose schedules and/or predictive biomarkers. Accordingly, the data from the expansion cohorts did not meet Genmab’s stringent criteria for proof-of-concept.

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

Vas Narasimhan's 'Wild Card' drugs: No­var­tis CEO high­lights po­ten­tial jack­pots, as well as late-stage stars, in R&D pre­sen­ta­tion

Novartis is always one of the industry’s biggest R&D spenders. As they often do toward the end of each year, company execs are highlighting the drugs they expect will most likely be winners in 2021.

And they’re also dreaming about some potential big-time lottery tickets.

As part of its annual investor presentation Tuesday, where the company allows investors and analysts to virtually schmooze with the bigwigs, Novartis CEO Vas Narasimhan will outline what he thinks are the pharma’s “Wild Cards.” The slate of five experimental drugs are those that Novartis hopes can be high-risk, high-reward entrants into the market over the next half-decade or so, and cover a wide range of indications.

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The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

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John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

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