In a squeak­er, FDA Ad­Comm votes for an OK of Cem­pra’s an­tibi­ot­ic

Bri­an Sko­r­ney, Baird an­a­lyst

Cem­pra $CEMP just bare­ly squeaked through an Ad­Comm re­view for its pro­posed new an­tibi­ot­ic solithromycin on Fri­day, with a slim ma­jor­i­ty of 7 to 6 cast­ing votes in its fa­vor on the key ques­tion of whether the ben­e­fits out­weighed the ob­vi­ous tox­i­c­i­ty risks as­so­ci­at­ed with their prod­uct.

Past safe­ty is­sues as­so­ci­at­ed with telithromycin (Ketek) clear­ly weighed on all the mem­bers, but with grow­ing re­sis­tance to ex­ist­ing an­tibi­otics be­com­ing an ever-grow­ing pub­lic health cri­sis, there were enough ‘yes’ votes to get this one over the line.

Next stop: The FDA has to make the for­mal de­ci­sion, and it’s like­ly to con­sid­er this vote as a vir­tu­al split, leav­ing it in the po­si­tion of ei­ther throw­ing up the stop sign, or sign­ing on with a lot of strings at­tached to an ap­proval.

The com­mit­tee fre­quent­ly ze­roed in on the crux of the is­sue: New an­tibi­otics are bad­ly need­ed and solithromycin al­so met the piv­otal end­point on non-in­fe­ri­or­i­ty. But the an­timi­cro­bial drugs ad­vi­so­ry group had to bal­ance that against trou­bling signs of liv­er tox­i­c­i­ty that could harm pa­tients. And an­a­lysts were left skep­ti­cal that Cem­pra, even if it gets a for­mal OK, would be able to ef­fec­tive­ly mar­ket it. Not­ed Baird’s Bri­an Sko­r­ney:

(A)s we out­lined in our down­grade note, mar­ket­ing re­stric­tions are like­ly to be so bur­den­some, if ap­proved, based on pan­elists con­cerns over drug-in­duced liv­er in­jury and the unan­i­mous re­quests to re­strict and mon­i­tor it, the com­mer­cial po­ten­tial could be neg­li­gi­ble. Al­though we ex­pect the stock to give up some of its loss­es on short cov­er­ing, we con­tin­ue to see the soli op­por­tu­ni­ty as fun­da­men­tal­ly im­paired by safe­ty con­cerns.

How would Cem­pra track cas­es and what could they do to re­duce risks af­ter sev­er­al ad­verse events were record­ed in its tri­als?

These were three key ques­tions:

  • Did the biotech pro­vide suf­fi­cient ef­fi­ca­cy da­ta for treat­ing com­mu­ni­ty-ac­quired bac­te­r­i­al pneu­mo­nia?

The vote was unan­i­mous, 13 to 0 in fa­vor of solithromycin.

Marc Scheetz, a phar­ma­cist, felt that the an­tibi­ot­ic should be rig­or­ous­ly lim­it­ed to 5 to 7 days of ther­a­py but agreed with the rest of the com­mit­tee that the ef­fi­ca­cy da­ta were clear and that the an­tibi­ot­ic works as billed. Sev­er­al com­mit­tee mem­bers called the da­ta ad­e­quate, but not nec­es­sar­i­ly sub­stan­tial.

  • Was the risk of he­pa­tox­i­c­i­ty prop­er­ly char­ac­ter­ized?

The vote went the oth­er way, 12 to 1 vot­ing ‘no.’ Small sam­ple sizes in the tri­als drew some sharp re­spons­es and many of the com­mit­tee mem­bers were clear­ly con­cerned about how this should be dealt with in the re­al world. For sev­er­al pan­el mem­bers, the ques­tion seemed to bal­ance on whether Cem­pra should be re­quired to get a bet­ter un­der­stand­ing of the an­tibi­ot­ic in Phase III or Phase IV, af­ter an ap­proval.

Sev­er­al com­mit­tee mem­bers — though cer­tain­ly not all — leaned to­ward a Phase IV, which would re­quire a larg­er study, a point that was echoed by oth­ers.

  • Do the ben­e­fits out­weigh the risk?

This was the mon­ey shot, and it just bare­ly fell in­to Cem­pra’s fa­vor.

Tom Boy­er vot­ed no. If there was no oth­er op­tion, he’d say yes, but the risk of tox­i­c­i­ty clear­ly out­weighed the ben­e­fit.

Marc Scheetz: Yes, but… “I wish I could have vot­ed the mean, or maybe.” And its use should be se­vere­ly re­strict­ed un­til more da­ta is gath­ered.

Ellen An­drews says the bugs just won’t stop, and that’s what swayed her vote in fa­vor of an ap­proval, in spite of the risk.

The re­view to­day marks a crit­i­cal junc­ture for a hand­ful of biotechs with late-stage an­tibi­otics. The path to mar­ket is clear, as are the ob­sta­cles in the clin­ic. None of that change to­day.

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.