Lil­ly's ap­proved can­cer drug Lartru­vo fails con­fir­ma­to­ry study, set­ting the stage for with­draw­al of reg­u­la­to­ry en­dorse­ment

Back in 2016, Lil­ly won FDA ac­cel­er­at­ed ap­proval for its soft tis­sue drug olara­tum­ab on the ba­sis of en­cour­ag­ing da­ta from a small 133-pa­tient mid-stage study, but on Fri­day a larg­er, con­fir­ma­to­ry tri­al meant to ce­ment the ap­proval showed that the treat­ment failed to help pa­tients live longer, which means the US health reg­u­la­tor can re­scind its en­dorse­ment of the drug.

The drug, sold as Lartru­vo, had won the FDA nod in com­bi­na­tion with the chemother­a­py dox­oru­bicin as a first-line treat­ment for a sub­set of pa­tients with the dis­ease, which had seen no new ap­provals in decades. By the third quar­ter of 2018, Lil­ly had raked in $221.2 mil­lion in Lartru­vo sales last year.

The con­fir­ma­to­ry Phase III tri­al — AN­NOUNCE — test­ed Lartru­vo in com­bi­na­tion with dox­oru­bicin, ver­sus dox­oru­bicin monother­a­py in pa­tients with ad­vanced or metasta­t­ic soft tis­sue sar­co­ma. The study did not meet the main goal of im­prov­ing over­all sur­vival in the pa­tient pop­u­la­tion, in­clud­ing the sub­set of leiomyosar­co­ma pa­tients — there was no dif­fer­ence in sur­vival be­tween the study arms for ei­ther pop­u­la­tion, the com­pa­ny said.

Anne White

Da­ta from the pre­vi­ous, pos­i­tive Phase II tri­al had helped Lil­ly se­cure ac­cel­er­at­ed ap­proval in the Unit­ed States, and con­di­tion­al ap­proval in Eu­rope. But those ap­provals were con­tin­gent on fa­vor­able AN­NOUNCE re­sults con­firm­ing its ben­e­fit, and now the com­pa­ny will talk to reg­u­la­tors to de­ter­mine the next steps for the drug.

For now, the drug­mak­er has sus­pend­ed Lartru­vo pro­mo­tion, and ex­pects to in­cur a pre-tax charge in the range of $70 mil­lion to $90 mil­lion (or $0.10 per share, af­ter tax) in the first quar­ter of 2019.

“Lil­ly was sur­prised and dis­ap­point­ed that LARTRU­VO did not im­prove sur­vival for pa­tients with ad­vanced soft tis­sue sar­co­ma in this study,” said Anne White, pres­i­dent of Lil­ly On­col­o­gy in a state­ment. Lil­ly’s $LLY shares slipped about 3% pre-mar­ket.

The drug is cur­rent­ly al­so be­ing test­ed in com­bi­na­tion with gem­c­itabine and do­c­etax­el in a sep­a­rate Phase II tri­al in ad­vanced soft tis­sue sar­co­ma pa­tients.

The fail­ure fol­lows Lil­ly’s an­nounce­ment this month to swal­low Loxo On­col­o­gy for $8 bil­lion. Ac­cord­ing to a SEC fil­ing post­ed on Thurs­day, Lil­ly ex­ec­u­tives were look­ing for a swift deal when they sat down with Loxo CEO Josh Bilenker five days ahead of Christ­mas. They were will­ing to fork out $230 a share for the small­er com­pa­ny, in a hur­ry to get the deal done in time for the JP­Mor­gan ex­trav­a­gan­za. There were no oth­ers bid­ders for the com­pa­ny, but in or­der to has­ten the buy­out, Lil­ly agreed even­tu­al­ly to pay $235 per Loxo share, al­low­ing for the ac­qui­si­tion to be re­vealed on Jan­u­ary 7.

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.