Mer­ck pulls the plug on a study eval­u­at­ing block­buster Keytru­da with Yer­voy for NSCLC

About a month ago, up­on tout­ing new on­col­o­gy da­ta, Mer­ck reaf­firmed its com­mit­ment to ex­plor­ing new Keytru­da com­bi­na­tions for lung can­cer pa­tients. The Big Phar­ma has now pulled the plug on one of those com­bi­na­tions, af­ter in­ter­im da­ta showed an in­creased risk and no re­ward.

An in­de­pen­dent Da­ta Mon­i­tor­ing Com­mit­tee urged Mer­ck to end a Phase III tri­al eval­u­at­ing cash cow Keytru­da — which brought in $11.1 bil­lion last year — and Bris­tol My­ers Squibb’s Yer­voy (ip­il­i­mum­ab) in PD-L1 pos­i­tive metasta­t­ic non-small cell lung can­cer (NSCLC) pa­tients. In an in­ter­im analy­sis, the com­bi­na­tion showed no in­cre­men­tal ben­e­fit in over­all sur­vival (OS) or pro­gres­sion-free sur­vival (PFS), the study’s two pri­ma­ry end­points.

To make mat­ters worse, the com­bo was linked to a high­er in­ci­dence of side ef­fects, in­clud­ing se­ri­ous ad­verse events and ad­verse events lead­ing to “dis­con­tin­u­a­tion or death,” com­pared to the Keytru­da monother­a­py, ac­cord­ing to Mer­ck.

A to­tal of 568 pa­tients re­ceived ei­ther 200 mg of Keytru­da in­tra­venous­ly once every three weeks for up to 35 cy­cles and 1 mg/kg IV of Yer­voy once every six weeks for up to 18 cy­cles, or the same amount of Keytru­da with a place­bo. The full da­ta are com­ing at a fu­ture sci­en­tif­ic con­gress, and will be re­port­ed to reg­u­la­tors, the com­pa­ny an­nounced.

Roy Baynes

“It is very clear that in this study, the ad­di­tion of ip­il­i­mum­ab did not add clin­i­cal ben­e­fit but did add tox­i­c­i­ty. Keytru­da monother­a­py re­mains a stan­dard of care for the treat­ment of cer­tain pa­tients with metasta­t­ic non-small cell lung can­cer whose tu­mors ex­press PD-L1,” Roy Baynes, CMO and head of glob­al clin­i­cal de­vel­op­ment at Mer­ck Re­search Lab­o­ra­to­ries, said in a state­ment.

Bris­tol My­ers Squibb didn’t take the jab light­ly, and fol­lowed up with End­points News to em­pha­size that its own PD-1, Op­di­vo, pairs quite well with Yer­voy.

“Check­Mate -227, Check­Mate -9LA and Keynote -598 are all dif­fer­ent tri­als, with dif­fer­ent pa­tient pop­u­la­tions, com­para­tors, end­points and du­ra­tions of fol­low-up. For ex­am­ple, Check­Mate -227 and Check­Mate -9LA en­rolled pa­tients across PD-L1 ex­pres­sion lev­els and his­tolo­gies. Keynote -598 on­ly en­rolled pa­tients with PD-L1 ex­pres­sion ≥50%,” a spokesper­son said.

While Yer­voy has been ap­proved with an an­ti-PD-1 ther­a­py in some in­di­ca­tions, most stud­ies sup­port­ing those ap­provals didn’t com­pare the com­bi­na­tion di­rect­ly to the an­ti-PD-1 monother­a­py, ac­cord­ing to Mer­ck. Back in May, Op­di­vo and Yer­voy got a land­mark NSCLC ap­proval ap­proval for PD-L1 pos­i­tive pa­tients — but the tri­al com­pared the com­bi­na­tion to treat­ment with plat­inum-dou­blet chemother­a­py. Days lat­er, the com­bo was al­so ap­proved in com­bi­na­tion with a lim­it­ed course of chemother­a­py.

In Check­Mate-915, re­searchers did eval­u­ate Op­di­vo and Yer­voy against Op­di­vo alone in ad­ju­vant melanoma pa­tients. How­ev­er, they found that the com­bi­na­tion didn’t achieve a sig­nif­i­cant im­prove­ment in re­cur­rence-free sur­vival (RFS) in the all-com­er pop­u­la­tion.

“We re­main com­mit­ted to con­tin­ued re­search in melanoma, both to fur­ther un­der­stand the po­ten­tial ben­e­fit of Yer­voy in com­bi­na­tion with Op­di­vo to treat high-risk melanoma pa­tients in the ear­li­er stages of dis­ease, as well as to study ad­di­tion­al nov­el com­bi­na­tions in var­i­ous set­tings,” Bris­tol My­ers Squibb VP and head of on­col­o­gy clin­i­cal de­vel­op­ment Sabine Maier said in a state­ment at the time.

Keytru­da is al­ready ap­proved to treat a va­ri­ety of can­cers aside from NSCLC, in­clud­ing small cell lung can­cer, melanoma, head and neck squa­mous cell can­cer, and Hodgkin lym­phoma, to name a few. Yer­voy is ap­proved for un­re­sectable or metasta­t­ic melanoma, and in com­bi­na­tion with Op­di­vo for sev­er­al can­cers, in­clud­ing NSCLC, mis­match re­pair de­fi­cient metasta­t­ic col­orec­tal can­cer, ad­vanced re­nal cell car­ci­no­ma and he­pa­to­cel­lu­lar car­ci­no­ma.

Back in May, Roche’s Tecen­triq got FDA ap­proval to treat new­ly di­ag­nosed, metasta­t­ic NSCLC pa­tients with­out EGFR or ALK mu­ta­tions whose tu­mors have high PD-L1 ex­pres­sion. “By virtue of be­ing late to mar­ket, Tecen­triq monother­a­py (IM­POW­ER110) has lit­tle chance of gain­ing sig­nif­i­cant share in 1L NSCLC de­spite post­ing OS sim­i­lar to Keytru­da in PD-L1 high pa­tients,” Cowen an­a­lyst Steve Scala wrote to in­vestors that month.

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

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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