Ab­b­Vie gets a big boost in the ma­jor league rheuma­toid arthri­tis fi­nals with promis­ing PhI­II da­ta

Ab­b­Vie passed on a big part­ner­ship it had set up with Gala­pa­gos on the promis­ing rheuma­toid arthri­tis drug fil­go­tinib so it could fo­cus all of its ef­forts on an in-house pro­gram for upadac­i­tinib (ABT-494). And to­day the block­buster gam­ble was re­ward­ed with a round of stel­lar da­ta from their first Phase III study of the oral JAK in­hibitor.

Both the 15 mg and 30 mg dos­es swept the pri­ma­ry and sec­ondary end­points in the study, with 64% and 66% re­spec­tive­ly hit­ting ACR20, with a min­i­mum 20% im­prove­ment in the dis­ease score.  ACR50 came in at 38% and 43%. Low dis­ease ac­tiv­i­ty was marked by about half of the pa­tients while on­ly 17% of the place­bo arm could say the same.

Here’s the full chart:

There have been a host of ma­jor league ri­vals go­ing af­ter RA re­cent­ly, with mixed re­sults. So how does ABT-494 stack up?

At the top of the set­back list is Eli Lil­ly’s baric­i­tinib, part­nered with In­cyte, which the FDA re­ject­ed in April for large­ly un­known rea­sons. J&J and Glax­o­SmithK­line re­cent­ly stum­bled in a head-to-head with sirukum­ab against Hu­mi­ra, a main­stay in the mar­ket. The 50 mg and 100 mg sirukum­ab num­bers hit 27% and 35% on ACR50 com­pared to 32% of the Hu­mi­ra group. But Re­gen­eron and Sanofi scored with sar­ilum­ab (Kevzara), win­ning an ap­proval for the IL-6 drug re­cent­ly af­ter be­ing de­layed over man­u­fac­tur­ing is­sues.

Ab­b­Vie has high hopes for the oral upadac­i­tinib, wide­ly tapped as a block­buster-to-be. It’s al­ready well in­to a late-stage pro­gram on pso­ri­at­ic arthri­tis fol­lowed by Crohn’s dis­ease, ul­cer­a­tive col­i­tis and atopic der­mati­tis. And Ge­of­frey Porges at Leerink was quick to of­fer the com­pa­ny ku­dos for the way this ther­a­py is be­ing po­si­tioned. He not­ed:

The place­bo-ad­just­ed ACR20 ben­e­fit rates for upadac­i­tinib with methotrex­ate of 28%-30% are nu­mer­i­cal­ly su­pe­ri­or to com­peti­tor LLY (OP)/IN­CY’s (OP) baric­i­tinib of 22-26% in the same tri­al with pa­tients who had in­ad­e­quate re­spons­es to DMARD, and the more strin­gent place­bo-ad­just­ed ACR50 and ACR70 rates for upadac­i­tinib are al­so high­er than seen in the baric­i­tinib tri­al. We cur­rent­ly mod­el $1.6bn in peak sales for upadac­i­tinib com­pared to con­sen­sus ex­pec­ta­tions of $2.5bn in 2027E, and we be­lieve that the su­pe­ri­or da­ta and re­cent FDA re­jec­tion of baric­i­tinib fa­vor­ably po­si­tion Ab­b­Vie in the JAK mar­ket seg­ment, and could lead to ma­te­r­i­al up­side to fore­casts.

The phar­ma com­pa­ny was so pumped about its prospects with this drug, with peak sales pro­jec­tions run­ning in­to the bil­lions, that it walked away from its $150 mil­lion up­front on a ri­val oral ther­a­py, which Gilead quick­ly scooped up for it­self.

Gerd Burmester

“Achiev­ing the tar­get of low dis­ease ac­tiv­i­ty in near­ly half of the pa­tients by 12 weeks and do­ing so at both high and low dose lev­els is en­cour­ag­ing,” said Gerd Burmester, pro­fes­sor of med­i­cine, De­part­ment of Rheuma­tol­ogy and Clin­i­cal Im­munol­o­gy, Char­ité Berlin, in a state­ment. “Cur­rent treat­ment rec­om­men­da­tions rec­og­nize the im­por­tance of this clin­i­cal tar­get for pa­tients, as achiev­ing low dis­ease ac­tiv­i­ty has re­mained an un­met need in rheuma­toid arthri­tis.”

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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Pascal Soriot (AP Images)

UP­DAT­ED: 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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Covid-19 roundup: Eu­rope pur­chas­es 80M dos­es of Mod­er­na's vac­cine; CO­V­AXX se­cures $2.8B in emerg­ing mar­ket pre-or­ders

With the announcement of its vaccine efficacy data last week, Moderna is starting to line up customers for its Covid-19 mRNA jabs.

The Massachusetts-based biotech announced Wednesday it has agreed to sell an initial round of 80 million doses to the European Commission, with the option to double the amount to 160 million. Once the member states rubber stamp the approval, the deal will be finalized.

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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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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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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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