Se­vere ad­verse events mar the end of Roche’s PhI­II for ‘break­through’ he­mo­phil­ia drug

Daniel O’Day, Roche CEO

With Phase III da­ta loom­ing for its close­ly-watched he­mo­phil­ia drug ACE910 (emi­cizum­ab), Roche says that in­ves­ti­ga­tors have tracked four se­ri­ous cas­es of blood clot­ting among pa­tients tak­ing the ther­a­py. And the news im­me­di­ate­ly buoyed shares of both Shire and No­vo Nordisk, which are first in line for see­ing their fran­chis­es take a hit from the ex­per­i­men­tal ther­a­py.

Roche says that there were two cas­es of throm­boem­bol­ic events and two cas­es of throm­bot­ic mi­croan­giopa­thy among pa­tients with break­through bleed­ing who were be­ing treat­ed with Shire’s FEI­BA and No­vo’s Novo­Sev­en, by­pass­ing agents that car­ry a throm­bo­sis warn­ing, ac­cord­ing to Reuters.

Here’s the state­ment Roche sent to End­points News:

What we have so far are 4 spon­ta­neous­ly re­port­ed SAE (se­ri­ous ad­verse events). And these events were seen with the con­comi­tant use of mul­ti­ple dos­es of a by­pass­ing agent with emi­cizum­ab while treat­ing a break­through bleed; in some cas­es the by­pass­ing agent at dos­es ex­ceed­ing the rec­om­mend­ed la­beled dos­es.

In col­lab­o­ra­tion with our Steer­ing Com­mit­tee and IDMC, com­posed of well-rec­og­nized he­mo­phil­ia ex­perts, we have a risk mit­i­ga­tion strat­e­gy we be­lieve will be ef­fec­tive in re­duc­ing the risk of this type of ad­verse event and al­low us to gain more in­for­ma­tion to in­form our un­der­stand­ing of these safe­ty events.

The cur­rent rec­om­men­da­tion is to avoid the use of one spe­cif­ic by­pass­ing agent and if nec­es­sary, to use it start­ing with the low­er range of the rec­om­mend­ed la­beled dose and per­form dos­ing un­der mon­i­tor­ing.

Im­por­tant­ly, all of these ad­verse events have re­solved and two of the pa­tients have since restart­ed emi­cizum­ab and have not ex­pe­ri­enced a re­cur­rence of the ad­verse event to date.

Right now there’s no cer­tain­ty over what, if any, im­pact the ad­verse events will have on the drug’s fate, but any kind of cloud over the drug spells some im­me­di­ate re­lief for Shire and No­vo Nordisk, which has been par­tic­u­lar­ly un­der the gun re­cent­ly on the di­a­betes front. Bio­gen, mean­while, is spin­ning out its port­fo­lio of he­mo­phil­ia drugs.

No­vo Nordisk CEO Lars Re­bi­en Sørensen

Chief Ex­ec­u­tive Of­fi­cer Lars Re­bi­en Sørensen, known for mak­ing blunt com­ments, iden­ti­fied ACE910 as “the key threat” to its block­buster fran­chise, built around Novo­Sev­en, ac­cord­ing to an in-depth analy­sis from Bloomberg to­day. And Shire, which just ac­quired Bax­al­ta and its port­fo­lio of he­mo­phil­ia drugs, saw its shares spike on the Lon­don ex­change af­ter the first re­ports hit.

The news about these ad­verse events amounts to the first dent in ACE910’s for­mi­da­ble rep­u­ta­tion. Roche’s Daniel O’Day has been an out­spo­ken cham­pi­on for this drug, cit­ing it re­peat­ed­ly as one of the phar­ma gi­ant’s biggest late-stage pro­grams. And an­a­lysts have re­peat­ed­ly tapped it as a like­ly block­buster, able to gen­er­ate bil­lions in an­nu­al rev­enue.

Their drug—an an­ti-fac­tor IXa/X bis­pe­cif­ic which mim­ics the func­tion of Fac­tor VI­II, even in the pres­ence of FVI­II in­hibitors—is near­ing the end of a ma­jor, Roche-style Phase III pro­gram with a drug blessed by the FDA with a break­through drug des­ig­na­tion. Two Phase III stud­ies have be­gun in chil­dren and adults who have ac­quired Fac­tor VI­II in­hibitors. An­oth­er Phase III in pa­tients with­out the FVI­II in­hibitors is start­ing, and there’s a fourth Phase III planned for a once-every-4-weeks dose, to see if they can come up with an eas­i­er ad­min­is­tra­tion sched­ule than the once-week­ly in­jec­tion they’re work­ing with now.

In­ves­ti­ga­tors say that their fol­lowup of 18 pa­tients in the key proof of con­cept study re­vealed that emi­cizum­ab cut the bleed­ing rate of pa­tients by more than 95% af­ter a fol­lowup re­view last­ing up to 32.6 months long. And that’s what they ex­pect to prove in Phase III.

But ACE910 isn’t the on­ly break­through ther­a­py in the pipeline. Bio­Marin grabbed the spot­light at a ma­jor sci­en­tif­ic con­fer­ence last sum­mer with da­ta that nailed down hard ev­i­dence that its gene ther­a­py for he­mo­phil­ia A demon­strat­ed a high chance of restor­ing pa­tients’ nat­ur­al clot­ting abil­i­ties, re­duc­ing or elim­i­nat­ing bleed­ing episodes and point­ing them down the road to a nor­mal life. And com­pa­ny in­ves­ti­ga­tors are now hus­tling BMN 270 in­to a Phase IIb study that could be used to gain an ac­cel­er­at­ed ap­proval for a po­ten­tial block­buster.

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
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 costs in com­pa­ny-wide re­org

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy reveal tomorrow 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, 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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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.