Trad­ing places with Bris­tol-My­ers, Mer­ck hit with an­oth­er late-stage set­back on check­point star Keytru­da

Close to a year af­ter Mer­ck $MRK won an ac­cel­er­at­ed FDA OK to use its PD-1 check­point star Keytru­da for treat­ing sec­ond-line cas­es head and neck squa­mous cell car­ci­no­ma in com­bi­na­tion with plat­inum-con­tain­ing chemo, the phar­ma gi­ant an­nounced that its big Phase III study for that in­di­ca­tion failed.

The piv­otal KEYNOTE-040 tri­al failed to meet the pri­ma­ry end­point on over­all sur­vival in com­par­ing the block­buster check­point against stan­dard ther­a­pies, the phar­ma gi­ant re­port­ed. But the cur­rent ap­proval stands nev­er­the­less, Mer­ck said in a state­ment.

“The com­pa­ny not­ed that the FDA re­mains com­fort­able with the drug’s cur­rent ac­cel­er­at­ed ap­proval in this in­di­ca­tion de­spite the tri­al re­sults,” ob­served Leerink’s Sea­mus Fer­nan­dez. “Im­por­tant­ly, Keytru­da ap­pears to have an­oth­er shot on goal for full ap­proval in H&N can­cer, as the Keynote-048 study in first-line pa­tients could, if pos­i­tive, serve as the con­fir­ma­to­ry tri­al.”

Roger Perl­mut­ter, Mer­ck

Mer­ck didn’t pro­vide a lot of de­tails, but this is the lat­est in a se­ries of set­backs in the field that have be­gun to show the out­er lim­its of ef­fi­ca­cy for a new class of can­cer med that has trans­formed on­col­o­gy ther­a­py in the past two years. But right now, those out­er lim­its of ef­fi­ca­cy run along a blur­ry line, with no clear ex­pla­na­tions for what is caus­ing these sud­den break­downs.

Mer­ck re­cent­ly was forced to put a slate of 3 Keytru­da tri­als for mul­ti­ple myelo­ma on hold af­ter in­ves­ti­ga­tors spot­ted a high­er rate of death in the check­point arm. Two of those stud­ies used com­bi­na­tions with Cel­gene drugs, Po­m­a­lyst and its big drug Revlim­id.

Mer­ck has ini­ti­at­ed hun­dreds of stud­ies, in­clud­ing some 300 com­bi­na­tion stud­ies, as it races to cap­i­tal­ize on its new lead in the field af­ter Bris­tol-My­ers Squibb ran in­to se­ri­ous is­sues with a failed study for lung can­cer. It’s clear that af­ter see­ing some re­mark­able im­prove­ments for a sig­nif­i­cant mi­nor­i­ty of check­point pa­tients, these ther­a­pies have their lim­its. Roche has al­so had its own prob­lems with the fail­ure of a Phase III con­fir­ma­to­ry study us­ing Tecen­triq.

Bris­tol-My­ers’ Op­di­vo, mean­while, post­ed pos­i­tive Phase III da­ta on squa­mous cell car­ci­no­ma of the head and neck back in late 2016, with a me­di­an OS of 7.5 months for Op­di­vo com­pared to 5.1 months for in­ves­ti­ga­tor’s choice.

What to make of that?

“Up un­til yes­ter­day,” not­ed Ever­core ISI’s Umer Raf­fat, “I would have told you that there are at least 2 dif­fer­ent in­di­ca­tions where MRK worked and oth­ers failed … and per­haps MRK is just ex­e­cut­ing these tri­als much bet­ter.  How­ev­er, as of to­day, there ap­pears to be no con­sis­ten­cy in the in­con­sis­ten­cy.  Now MRK failed where BMY worked.”

“We are en­cour­aged by the pos­i­tive im­pact that KEYTRU­DA has had on many can­cer pa­tients, in­clud­ing those with pre­vi­ous­ly treat­ed re­cur­rent or metasta­t­ic head and neck can­cer, and we re­main con­fi­dent that KEYTRU­DA is an im­por­tant ther­a­py for this dif­fi­cult-to-treat can­cer,” said Roger Dansey, late-stage on­col­o­gy de­vel­op­ment leader, Mer­ck Re­search Lab­o­ra­to­ries. “We look for­ward to shar­ing the com­pre­hen­sive da­ta analy­sis from KEYNOTE-040 with the sci­en­tif­ic com­mu­ni­ty at an up­com­ing med­ical meet­ing.”

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.