Check­Mate-451: Bris­tol-My­ers’ Op­di­vo — plus Yer­voy — fails PhI­II com­bo lung can­cer study, the lat­est in a se­ries of set­backs

Bris­tol-My­ers Squibb $BMY is be­com­ing well prac­ticed at dis­ap­point­ing in­vestors with their R&D strat­e­gy for lung can­cer.

Af­ter the mar­ket closed Mon­day the phar­ma gi­ant re­port­ed that their Phase III tri­al match­ing Op­di­vo and their CT­LA-4 drug Yer­voy for Check­Mate-451 failed on the pri­ma­ry end­point for over­all sur­vival. Re­searchers were study­ing the com­bi­na­tion as a main­te­nance ther­a­py for small cell lung can­cer af­ter a first round of chemo, and this was one of the late-stage stud­ies that an­a­lysts have been wait­ing for.

Thomas Lynch, CSO at Bris­tol-My­ers Squibb, at a June 2018 End­points News pan­el in Boston
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The fail­ure fol­lows close on the heels of an­oth­er Phase III flop for their Check­Mate-331 study, where Op­di­vo was un­able to beat the stan­dard of care for treat­ing sec­ond-line small cell lung can­cer.

Cowen calls this a hard hit for Bris­tol-My­ers.

The fail­ure of CM-451 is a sig­nif­i­cant miss for BMY. With­out a 1L Op­di­vo + chemo com­bi­na­tion study as part of the de­vel­op­ment strat­e­gy, it ap­pears BMY is out of near-term op­por­tu­ni­ties to ad­vance Op­di­vo in­to 2L ther­a­py or 1L main­te­nance.

Bris­tol-My­ers re­strict­ed them­selves to a brief top-line an­nounce­ment to­day, sav­ing the ac­tu­al da­ta for lat­er. Their stock dropped close to 3% in af­ter-mar­ket trad­ing.

Bris­tol-My­ers’ set­back comes just two months af­ter Roche scored on IM­pow­er133 in SCLC. The key met­rics: Tecen­triq plus chemo hit a me­di­an over­all sur­vival rate of 12.3 months com­pared to 10.3 months for chemo alone — a sig­nif­i­cant 30% drop in the risk of death. The PFS hit 5.2 months ver­sus 4.3 months with a haz­ard ra­tion of a more mod­est 0.77. That’s not phe­nom­e­nal, but it’s an im­prove­ment in a niche not known for im­prove­ments.

The com­pa­ny had es­tab­lished an ear­ly lead over Mer­ck’s $MRK Keytru­da. But over the past few years Mer­ck’s R&D group has been steadi­ly mak­ing progress in the block­buster ri­val­ry, re­cent­ly pass­ing Bris­tol-My­ers in quar­ter­ly rev­enue and putting it­self on track to widen the gap. 

More re­cent­ly Bris­tol-My­ers has been look­ing to es­tab­lish a niche for it­self with cas­es in­volv­ing a high tu­mor mu­ta­tion bur­den, but they are fac­ing some stiff head­winds on that quest.

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Roger Perlmutter, Merck

#ASH19: Here’s why Mer­ck is pay­ing $2.7B to­day to grab Ar­Qule and its next-gen BTK drug, lin­ing up Eli Lil­ly ri­val­ry

Just a few months after making a splash at the European Hematology Association scientific confab with an early snapshot of positive data for their BTK inhibitor ARQ 531, ArQule has won a $2.7 billion buyout deal from Merck.

Merck is scooping up a next-gen BTK drug — which is making a splash at ASH today — from ArQule in an M&A pact set at $20 a share $ARQL. That’s more than twice Friday’s $9.66 close. And Merck R&D chief Roger Perlmutter heralded a deal that nets “multiple clinical-stage oral kinase inhibitors.”

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Paul Hudson. Sanofi

New Sanofi CEO Hud­son adds next-gen can­cer drug tech to the R&D quest, buy­ing Syn­thorx for $2.5B

When Paul Hudson lays out his R&D vision for Sanofi tomorrow, he will have a new slate of interleukin therapies and a synthetic biology platform to boast about.

The French pharma giant announced early Monday that it is snagging San Diego biotech Synthorx in a $2.5 billion deal. That marks an affordable bolt-on for Sanofi but a considerable return for Synthorx backers, including Avalon, RA Capital and OrbiMed: At $68 per share, the price represents a 172% premium to Friday’s closing.

Synthorx’s take on alternative IL-2 drugs for both cancer and autoimmune disorders — enabled by a synthetic DNA base pair pioneered by Scripps professor Floyd Romesberg — “fits perfectly” with the kind of innovation that he wants at Sanofi, Hudson said.

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Game on: Re­gen­eron's BC­MA bis­pe­cif­ic makes clin­i­cal da­ta de­but, kick­ing off mul­ti­ple myelo­ma matchup with Bris­tol-My­ers

As J&J attempts to jostle past Bristol-Myers Squibb and bluebird for a landmark approval of its anti-BCMA CAR-T — and while GlaxoSmithKline maps a quick path to the FDA riding on its own BCMA-targeting antibody-drug conjugates — the bispecifics are arriving on the scene to stake a claim for a market that could cross $10 billion per year.

The main rivalry in multiple myeloma is shaping up to be one between Regeneron and Bristol-Myers, which picked up a bispecific antibody to BCMA through its recently closed $74 billion takeover of Celgene. Both presented promising first-in-human data at the ASH 2019 meeting.

FDA lifts hold on Abeon­a's but­ter­fly dis­ease ther­a­py, paving way for piv­otal study

It’s been a difficult few years for gene and cell therapy startup Abeona Therapeutics. Its newly crowned chief Carsten Thiel was forced out last year following accusations of unspecified “personal misconduct,” and this September, the FDA imposed a clinical hold on its therapy for a form of “butterfly” disease. But things are beginning to perk up. On Monday, the company said the regulator had lifted its hold and the experimental therapy is now set to be evaluated in a late-stage study.

Roche faces an­oth­er de­lay in strug­gle to nav­i­gate Spark deal past reg­u­la­tors — but this one is very short

Roche today issued the latest in a long string of delays of its $4.3 billion buyout of Philadelphia-based Spark Therapeutics. The delay comes as little surprise — it is their 10th in as many months — as their most recent delay was scheduled to expire before a key regulatory deadline.

But it is notable for its length: 6 days.

Previous extensions had moved the goalposts by about 3 weeks to a month, with the latest on November 22 expiring tomorrow. The new delay sets a deadline for next Monday, December 16, the same day by which the UK Competition and Markets Authority has to give its initial ruling on the deal. And they already reportedly have lined up an OK from the FTC staff – although that’s only one level of a multi-step process.

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KalVis­ta's di­a­bet­ic mac­u­lar ede­ma da­ta falls short — will Mer­ck walk away?

Merck’s 2017 bet on KalVista Pharmaceuticals may have soured, after the UK/US-based biotech’s lead drug failed a mid-stage study in patients with diabetic macular edema (DME).

Two doses of the intravitreal injection, KVD001, were tested against a placebo in a 129-patient trial. Patients who continued to experience significant inflammation and diminished visual acuity, despite anti-VEGF therapy, were recruited to the trial. Typically patients with DME — the most frequent cause of vision loss related to diabetes — are treated with anti-VEGF therapies such as Regeneron’s flagship Eylea or Roche’s Avastin and Lucentis.

UP­DAT­ED: Ob­sE­va makes case for best-in-class hor­mone sup­pres­sive ther­a­py in pos­i­tive uter­ine fi­broid study

About a month after the Swiss biotech disclosed a failed late-stage study in its IVF program, ObsEva on Monday unveiled positive pivotal data on its experimental treatment for heavy menstrual bleeding triggered by uterine fibroids.

ObsEva in-licensed the drug, linzagolix, from Japan’s Kissei Pharmaceutical in 2015. Two doses of the drug (100 mg and 200 mg) were tested against a placebo in the 535-patient Phase III study, dubbed PRIMROSE 2, in patients who were both on and off hormonal add-back therapy (ABT).

Samit Hirawat. Bristol-Myers Squibb

Bris­tol-My­ers is mak­ing a bee-line to the FDA with pos­i­tive liso-cel da­ta — but is it too late in the CAR-T game?

Bristol-Myers Squibb came to ASH this past weekend with a variety of messages on the new cancer drugs they had acquired in the big Celgene buyout, including liso-cel, the lead CAR-T program picked up in the $9 billion Juno acquisition. And one of the most important was that they had the pivotal efficacy and safety data needed to snag an approval from the FDA next year, with the BLA on track for a filing this month.