NASH con­tender CymaBay runs in­to trou­ble as mid-stage da­ta dis­ap­point

A snap­shot of neg­a­tive da­ta from an on­go­ing 52-week mid-stage NASH study eval­u­at­ing CymaBay Ther­a­peu­tics’ lead drug has trig­gered alarm, af­ter the ex­per­i­men­tal liv­er drug, se­ladel­par, per­formed worse than a place­bo at a three-month read­out.

Sur­prised and aghast, in­vestors of the San Fran­cis­co-based biotech wast­ed lit­tle time in reg­is­ter­ing their dis­ap­point­ment. The com­pa­ny’s shares $CBAY plum­met­ed about 44.5% to $6.16 in ear­ly Tues­day trad­ing.

In the 181-pa­tient tri­al, pa­tients were ei­ther giv­en place­bo, se­ladel­par 10 mg, 20 mg, or 50 mg once dai­ly. The main goal at the end of 12 weeks was to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in liv­er fat con­tent. Pa­tients giv­en the place­bo saw a re­duc­tion of 20.8% in liv­er fat, while those giv­en the three es­ca­lat­ing dos­es of se­ladel­par ex­pe­ri­enced small­er im­prove­ments: 10 mg (9.8%), 20 mg (14.2%) and 50 mg (13%).

Cymabay has pre­vi­ous­ly said it ex­pect­ed to see a 20-30% rel­a­tive — place­bo-ad­just­ed — change in liv­er fat at 12 weeks.

Pol Boudes Linkedin

“While the re­duc­tions in liv­er fat were min­i­mal, we re­main en­cour­aged by the sig­nif­i­cant im­prove­ments in bio­chem­i­cal mark­ers of liv­er in­jury…” Pol Boudes, CymaBay’s chief med­ical of­fi­cer, said in a state­ment.

The ex­per­i­men­tal drug’s 52-week biop­sy read­out is ex­pect­ed in mid-2020. Se­ladel­par be­longs to a fam­i­ly of drugs that ac­ti­vate pro­teins called per­ox­i­some pro­lif­er­a­tor-ac­ti­vat­ed re­cep­tors (PPARs), which reg­u­late gene ex­pres­sion. Ex­ist­ing ev­i­dence sug­gests that in the liv­er, PPAR ag­o­nists play a role in bile acid syn­the­sis, in­flam­ma­tion, fi­bro­sis and lipid me­tab­o­lism.

“While there is still a 52-week fol­low-up, we be­lieve that these 12-week re­sults sig­nif­i­cant­ly lessen the com­pet­i­tive threat of se­ladel­par in NASH. Hence, by less­en­ing the com­pet­i­tive threat, we be­lieve these re­sults should ben­e­fit In­ter­cept, as OCA re­mains the on­ly med­ica­tion to show a ben­e­fit on fi­bro­sis in a Phase 3 tri­al. While OCA has some is­sues of its own, we think it is no­table that one of those is NOT a failed ran­dom­ized, place­bo con­trolled study,” Baird’s Bri­an Sko­r­ney wrote in a note.

Akin to CymaBay, French drug de­vel­op­ers Gen­fit (set to re­port piv­otal da­ta in 2019) and In­ven­ti­va are work­ing on their own PPAR ag­o­nists for NASH.

On Tues­day morn­ing, shares of Gen­fit $GN­FT — that re­cent­ly made its Nas­daq de­but — were al­so down about 15% at $20.37. The move­ment like­ly re­flects in­vestors tak­ing the CymaBay da­ta as ev­i­dence against the ef­fi­ca­cy of Gen­fit’s elafi­bra­nor, Sko­r­ney not­ed. “We think this move is some­what un­jus­ti­fied…the two med­ica­tions were thought to have dif­fer­en­ti­at­ed mech­a­nisms of ac­tion, it seems that this may not be the case, as se­ladel­par’s da­ta sug­gest that the med­ica­tion does not re­duce liv­er fat, which is sim­i­lar to what we have seen from ear­li­er tri­als of elafi­bra­nor.”

How­ev­er, as a con­se­quence of the new CymaBay da­ta, the two PPAR ag­o­nists now look more sim­i­lar than dif­fer­ent, he said. “CymaBay may be at a sig­nif­i­cant dis­ad­van­tage mov­ing for­ward as we be­lieve that even if PPAR ag­o­nism is suc­cess­ful in Gen­fit’s Phase 3 tri­al, with­out any clear signs of dif­fer­en­ti­a­tion, CymaBay may have an up­hill bat­tle as they work to catch up to Gen­fit in NASH. If elafi­bra­nor fails in NASH, it would prob­a­bly be pre­dic­tive of the out­come of se­ladel­par in NASH. Ei­ther way, we think this makes the PPAR class, as a whole, look like a less sig­nif­i­cant com­pet­i­tive threat to OCA.”

Oth­er ma­jor NASH con­tenders — Gilead $GILD (fail in Phase III) and In­ter­cept $ICPT (mixed win in Phase III) — have dis­closed the top line num­bers of their late-stage tri­als. In­ter­cept is poised to sub­mit its mar­ket­ing ap­pli­ca­tion lat­er this year.

Im­age: Shut­ter­stock

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 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.