As­traZeneca, Mer­ck win red car­pet treat­ment at the FDA as a 3-time los­er seeks speedy OK for rare tu­mors

As­traZeneca’s R&D group doesn’t take fail­ure ly­ing down.

Hit with piv­otal set­backs for their MEK 1/2 in­hibitor selume­tinib in sev­er­al can­cer stud­ies, they re­grouped and in­clud­ed it in their $8.4 bil­lion al­liance with Mer­ck as the ther­a­py was steered in­to a Phase II for rare cas­es of neu­rofi­bro­mato­sis type 1, or NF1.

That da­ta gave the phar­ma gi­ant a break­through drug des­ig­na­tion in the spring, and now they are on track for a Q2 2020 PDU­FA af­ter the FDA added a pri­or­i­ty re­view to the gift pack­age to­day.

By in­hibit­ing the MEK en­zyme in the RAS/MAPK path­way in­ves­ti­ga­tors have demon­strat­ed that the drug can con­trol er­rant sig­nal­ing that con­trols cell growth — at least rel­e­vant to NF1.

Back in 2018, when Ned Sharp­less was run­ning the Na­tion­al Can­cer In­sti­tute — and where he’s head­ed back af­ter a stint as act­ing di­rec­tor of the FDA — he held up the re­search work on selume­tinib to a House com­mit­tee as one of the most im­por­tant projects in their can­cer moon­shots pro­gram, cit­ing the be­fore-and-af­ter pic­tures from par­ents with kids suf­fer­ing from in­op­er­a­ble tu­mors sparked by the dis­ease.

Ac­cord­ing to a re­port from the Chil­dren’s Tu­mor Foun­da­tion, which in­vest­ed in the pre­clin­i­cal work, in­ves­ti­ga­tors tracked a 70% re­sponse rate, with tu­mors shrink­ing at least 20%.

Pas­cal So­ri­ot As­traZeneca

Five years ago, as As­traZeneca CEO Pas­cal So­ri­ot pledged to make As­traZeneca in­to a roar­ing suc­cess with $45 bil­lion in an­nu­al sales while fend­ing off a takeover at­tempt by Pfiz­er, selume­tinib loomed large among the ex­per­i­men­tal drugs he tagged for a block­buster fu­ture. Then the fail­ures start­ed to mount.

As­traZeneca was forced to con­cede 3 years ago that the drug flopped in KRAS-pos­i­tive non-small cell lung can­cer. Selume­tinib whiffed on pro­gres­sion-free sur­vival and failed to score on over­all sur­vival as well. And As­traZeneca had to walk away from the first Phase III for selume­tinib in 2015 af­ter the drug — in-li­censed from Ar­ray — failed for an eye can­cer called uveal melanoma. Most re­cent­ly the drug failed a Phase III study for dif­fer­en­ti­at­ed thy­roid can­cer in the sum­mer of 2018.

A win here would be sweet for the resur­gent on­col­o­gy team at As­traZeneca, which has fu­eled As­traZeneca’s long-await­ed come­back over the past year with big suc­cess­es for Lyn­parza, Tagris­so and to a more lim­it­ed ex­tent for the PD-L1 Imfinzi.

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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