As­traZeneca's di­a­betes drug Farx­i­ga cuts risk of CV death or wors­en­ing of heart fail­ure by 26% in land­mark study

About two weeks af­ter As­traZeneca’s $AZN un­veiled its di­a­betes treat­ment Farx­i­ga cut the risk of CV death or the wors­en­ing of heart fail­ure in pa­tients with heart dis­ease, in a land­mark tri­al — over the week­end the British drug­mak­er pre­sent­ed de­tailed da­ta at the Eu­ro­pean So­ci­ety of Car­di­ol­o­gy (ESC) Con­gress in Paris.

The re­sults em­anat­ed from the 4,744-pa­tient DA­PA-HF tri­al, which test­ed Farx­i­ga in pa­tients with re­duced ejec­tion frac­tion (HFrEF) — in which the heart mus­cle is not able to con­tract am­ply and, there­fore, ex­pels less oxy­gen-rich blood in­to the body — on stan­dard of care treat­ment, in­clud­ing those with and with­out type-II di­a­betes.

Farx­i­ga re­duced the com­pos­ite end­point of car­dio­vas­cu­lar (CV) death or wors­en­ing of heart fail­ure by 26% (p<0.0001) — in­clud­ing a re­duc­tion in each of the in­di­vid­ual com­po­nents of the end­point. Da­ta showed there was a 30% de­crease (p<0.0001) in the risk of ex­pe­ri­enc­ing a first episode of wors­en­ing heart fail­ure and an 18% cut (p=0.0294) in the risk of death from car­dio­vas­cu­lar caus­es.

John Mc­Mur­ray Uni­ver­si­ty of Glas­gow

Farx­i­ga “did all the things we would like any drug to do in heart fail­ure, which are to im­prove symp­toms, re­duce hos­pi­tal ad­mis­sions and in­crease sur­vival. Even bet­ter, Farx­i­ga was as ef­fec­tive in heart fail­ure pa­tients with­out di­a­betes as in those with di­a­betes,” John Mc­Mur­ray of the Uni­ver­si­ty of Glas­gow said in a state­ment on Sun­day.

Pa­tients with di­a­betes are of­ten af­flict­ed with oth­er co­mor­bidi­ties, such as obe­si­ty, CV dis­ease and kid­ney prob­lems. SGLT2 mak­ers have been vy­ing for a big­ger mar­ket share by dif­fer­en­ti­at­ing their drugs on the ba­sis of ther­a­peu­tic im­pact on re­nal im­pair­ment — but the ma­jor, most lu­cra­tive bat­tle­ground is the heart.

Farx­i­ga, akin to J&J’s $JNJ In­vokana and Eli Lil­ly’s $LLY Jar­diance, be­long to a class of di­a­betes drugs called sodi­um-glu­cose co-trans­porter 2 (SGLT2) in­hibitors, which work by curb­ing the ab­sorp­tion of glu­cose via the kid­neys so that sur­plus glu­cose is ex­cret­ed through uri­na­tion.

Last year, As­traZeneca pre­sent­ed mixed da­ta on Farx­i­ga from a large study in type-II di­a­betes pa­tients at risk for CV dis­ease or es­tab­lished CV dis­ease. In the DE­CLARE-TI­MI 58 tri­al, which in­clud­ed more than 17,000 pa­tients, Farx­i­ga met one of the main goals by con­fer­ring a sta­tis­ti­cal­ly-sig­nif­i­cant re­duc­tion in the com­pos­ite end­point of hos­pi­tal­iza­tion for heart fail­ure or CV death. But it failed to clear the co-pri­ma­ry end­point of re­duc­ing ma­jor ad­verse car­dio­vas­cu­lar events (MACE) ver­sus place­bo.

Farx­i­ga, which was ap­proved for use in type-II di­a­betes back in 2014 — whose sales un­der­whelmed an­a­lyst ex­pec­ta­tions in the sec­ond quar­ter — is al­so be­ing de­vel­oped for pa­tients with heart fail­ure in the DE­LIV­ER (HF­pEF) and DE­TER­MINE (HFrEF and HF­pEF) tri­als, in ad­di­tion to chron­ic kid­ney dis­ease in the DA­PA-CKD tri­al. Its ri­vals are test­ing their di­a­betes of­fer­ings in a range of heart and kid­ney tri­als as well.

Months ago, In­vokana da­ta in­di­cat­ed the drug con­ferred car­dio­vas­cu­lar (CV) ben­e­fit in pa­tients who do and do not have pre­ex­ist­ing CV dis­ease.

So­cial im­age: As­traZeneca, AP Im­ages

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.

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus -- chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

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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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Left top to right: Mark Timney, Alex Denner, Vas Narasimhan. (The Medicines Company, Getty, AP/Endpoints News)

In a play-by-play of the $9.7B Med­Co buy­out, No­var­tis ad­mits it over­paid while of­fer­ing a huge wind­fall to ex­ecs

A month into his tenure at The Medicines Company, new CEO Mark Timney reached out to then-Novartis pharma chief Paul Hudson: Any interest in a partnership?

No, Hudson told him. Not now, at least.

Ten months later, Hudson had left to run Sanofi and Novartis CEO Vas Narasimhan was paying $9.7 billion for the one-drug biotech – the largest in the string of acquisitions Narasimhan has signed since his 2017 appointment.

The deal was the product of an activist investor and his controversial partner working through nearly a year of cat-and-mouse negotiations to secure a deal with Big Pharma’s most expansionist executive. It represented a huge bet in a cardiovascular field that already saw two major busts in recent years and brought massive returns for two of the industry’s most eye-raising names.

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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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Jake Van Naarden, Josh Bilenker, Nisha Nanda (Credit: Loxo, Aisling Capital)

Josh Bilenker and his Loxo crew are tak­ing the reins on on­col­o­gy R&D at Eli Lil­ly, culling the weak and map­ping a new path

Josh Bilenker, Jake Van Naarden and Nisha Nanda came out of Eli Lilly’s $8 billion Loxo Oncology buyout with a bundle of cash and plenty of choices on what they could do next. Start a new company, go public. Live on the beach in 5-star luxury. Contemplate the stars — in their own observatory.

So what are they doing?

They formed a new executive team that is taking over the management of Eli Lilly’s hundreds-strong oncology R&D group — essentially using Loxo as a base for a bold new experiment in Big Pharma R&D in an attempt to create a true biotech environment with the deep pockets of a top-15 industry player. They’ve recruited David Hyman from Memorial Sloan Kettering to join the team as chief medical officer. And the mandate includes culling out the oncology pipeline, highlighting their star prospects and going after new programs wherever they can find the best prospects.

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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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