Af­ter get­ting beat up on its de­pres­sion drug pitch, a bat­tered Alk­er­mes piv­ots to schiz­o­phre­nia with a pos­i­tive PhI­II read­out — but skep­tics are ready to pounce

Bad­ly need­ing a new fo­cus af­ter reg­u­la­tors and ex­perts slapped around their pitch for the de­pres­sion drug ALKS-5461, Alk­er­mes $ALKS is chang­ing the top­ic to­day to schiz­o­phre­nia.

Craig Hop­kin­son

Thurs­day morn­ing the biotech out­fit laid claim to promis­ing da­ta from ALKS-3831, their new and im­proved com­bo of olan­za­p­ine/sami­dor­phan, flag­ging a hit on both co-pri­ma­ry end­points re­lat­ed to weight gain and a key sec­ondary they’re hop­ing will help sell the drug — with a mar­ket­ing ap­pli­ca­tion now on sched­ule for the FDA. But the skep­tics who have been siz­ing up Alk­er­mes’ am­bi­tions won­der if this drug can do well com­mer­cial­ly, which may ex­plain why their stock slipped slight­ly in the red in pre­mar­ket trad­ing.

The ef­fi­ca­cy end­points in this sec­ond Phase III study fo­cused on a low­er mean per­cent weight gain for schiz­o­phre­nia pa­tients tak­ing ‘3831 as well as a com­par­i­son with olan­za­p­ine on the num­ber of pa­tients who added 10% or more of their body weight go­ing in­to the study.

In the olan­za­p­ine group 29.8% of pa­tients gained 10% or more of body weight in 6 months com­pared to 17.8% for ALKS 3831; for the 7%-plus weight gain cat­e­go­ry it was 42.7% for olan­za­p­ine vs. 27.5% for ALKS 3831.

Richard Pops, Alk­er­mes

The p val­ues Alk­er­mes pre­sent­ed were all up­beat and sig­nif­i­cant, though the com­pa­ny plans to hold back many of the de­tails for a con­fer­ence. And it’s clear from a re­view of an­a­lysts’ com­ments in re­cent weeks that the de­tails will be im­por­tant in as­sess­ing whether or not Alk­er­mes has a drug that can fetch a brand­ed price in a field dom­i­nat­ed by cheap gener­ics.

They’re not hold­ing back a new drug ap­pli­ca­tion, though. That is slat­ed for a de­liv­ery date some­time at the mid-point of next year.

“Im­por­tant­ly, ALKS 3831 fa­vor­ably shift­ed the weight gain dis­tri­b­u­tion curve com­pared to olan­za­p­ine, both in terms of mean weight gain and pa­tients ex­pe­ri­enc­ing ex­treme weight gain,” said Craig Hop­kin­son, Alk­er­mes’ CMO. 

The tout­ing of this study will like­ly be in­tense as Alk­er­mes ex­ecs led by CEO Richard Pops look to turn in­vestors’ at­ten­tion away from the train wreck that ALKS-5461 has be­come. But it won’t be easy.

Leerink’s Marc Good­man ini­ti­at­ed cov­er­age a few days ago, con­clud­ing that ‘5461 was dead in the wa­ter af­ter a large ma­jor­i­ty of FDA ex­perts turned thumbs down on it in a re­cent re­view, which fol­lowed a scathing as­sess­ment of the da­ta and tri­al plan by FDA in­sid­ers. ‘3831 may get ap­proved, he added, but sell­ing a drug like this will be no easy mat­ter.

(W)e be­lieve that ex­pec­ta­tions are too high for ALKS-3831. MEDA­Corp physi­cians (and we) like this prod­uct, but we be­lieve re­im­burse­ment will be dif­fi­cult for a new brand with­out a nov­el mech­a­nism in a high­ly gener­ic mar­ket; (3) we don’t agree with the bull­ish stance by some in­vestors that the base busi­ness can jus­ti­fy the cur­rent val­u­a­tion for the whole com­pa­ny and thus the pipeline is viewed as a free wild­card.

Stifel’s Paul Mat­teis had this to say re­cent­ly:

We think the Street is mod­el­ing around a 40-50% prob­a­bil­i­ty-of-suc­cess for 4Q18 da­ta (we’re at 50%); “suc­cess” in it­self is sub­jec­tive though, as there’s a con­tin­u­um of out­comes here with re­spect to a sta­tis­ti­cal win vs. a com­mer­cial­ly-rel­e­vant sig­nal.

This Phase III is the mon­ey shot for Alk­er­mes. The re­search group al­ready pro­duced pos­i­tive Phase III da­ta un­der­scor­ing that their an­tipsy­chot­ic drug per­formed bet­ter than a place­bo while prov­ing sta­tis­ti­cal­ly about the same as gener­ic olan­za­p­ine alone. Weight gain is a rou­tine side ef­fect for their drug, but they’re look­ing to re­place a stan­dard ther­a­py with one that can guard a greater per­cent­age of pa­tients from putting on pounds dur­ing treat­ment.

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 $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.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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What does $6.9B buy these days in on­col­o­gy R&D? As­traZeneca has a land­mark an­swer

Given the way the FDA has been whisking through new drug approvals months ahead of their PDUFA date, AstraZeneca and their partners Daiichi Sankyo may not have to wait until Q2 of next year to get a green light on trastuzumab deruxtecan (DS-8201).

The pharma giant this morning played their ace in the hole, showing off why they were willing to commit to a $6.9 billion deal — with $1.35 billion in a cash upfront — to partner on the drug.

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Large advertisements for the drug Vivitrol decorate the walls of Grand Central Station on June 15, 2017 in New York City. (Photo: Andrew Lichtenstein via Getty)

FDA slaps down Alk­er­mes for mis­lead­ing Viv­it­rol ads — don't for­get vul­ner­a­bil­i­ty to opi­oid over­dose

The ads piqued interest as soon as they started appearing in 2016: at Grand Central Station, on the Red Line in Cambridge, and on a billboard off the New Jersey Turnpike. All showed a young person, generally with his or her arms crossed, and the question, “what is Vivitrol?”

Vivitrol’s maker, Alkermes, was in the midst of a marketing and lobbying campaign to promote the anti-opioid addiction drug — a campaign that would face significant backlash for tarnishing competitors despite little evidence for Vivitrol’s superiority.

FDA in-house re­view spot­lights an is­sue with one of Hori­zon's end­points but notes ef­fi­ca­cy for lead drug

The FDA in-house review highlights a disagreement of investigators’ use of a key endpoint by Horizon Pharma in the late-stage trial for the top drug in its pipeline, but largely agreed that the antibody was effective.

Horizon submitted a BLA for thyroid eye disease (TED) drug teprotumumab in March, less than two years after they bought the drug (and the rest of a division) from Narrow River for $145 million upfront. With breakthrough status, priority review, orphan designation and in-house sales projections of up to $750 million, the one-time Roche reject became the marquee pipeline asset for a company that’s developed some of the world’s most expensive drugs.

Seat­tle Ge­net­ics de­tails pos­i­tive OS and PFS da­ta for tu­ca­tinib in breast can­cer

Seattle Genetics $SGEN is showing off more positive data around tucatinib, its pivotal-stage drug for HER2 positive breast cancer.

A month after hearing about solidly upbeat hazard ratios, we learned today that the estimated progression-free survival rate at one year was 33% in the tucatinib arm compared to 12% for patients taking trastuzumab and capecitabine alone.

Median PFS was 7.8 months (95% CI: 7.5, 9.6) in the tucatinib arm, compared to 5.6 months (95% CI: 4.2, 7.1) in the control arm.

Bat­tered, cash hun­gry In­tec feels the burn of No­var­tis re­jec­tion

It’s a case of some bad timing for Intec.

Just when a key trial testing the company’s Accordion drug delivery tech imploded in Parkinson’s disease, they handed Novartis data from a successful PK study of a custom Accordion pill engineered to deliver a Novartis compound to entice the Swiss drugmaker into signing a licensing agreement.

Novartis said thanks, but no thanks.

For the cash-strapped Israeli drug developer, the failure to clinch the deal marks a big blow. As of the third quarter, the company has $15.7 million in cash and equivalents, which HC Wainwright analysts estimate will keep the lights on into mid-2020.

Bris­tol-My­ers shows off a low-pro­file AML con­tender it gained from Cel­gene buy­out — and they’re tak­ing it straight to the FDA

Bristol-Myers Squibb reaped an enormous pipeline with its much-criticized $64 billion megadeal to buy Celgene. And it got a few hidden gems in the deal.

One of those gems was brought out for display on Tuesday, with a late-breaker at ASH on CC-486, which is now being prepped for regulatory filings at the FDA and elsewhere.

Celgene top-lined the positive results in a maintenance setting for acute myeloid leukemia a few months ago, but at ASH investigators pulled back the curtains on the all-important data they believe will give them an advantage in the commercial wars to come.

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De­sert­ed by Astel­las and Mer­ck, lit­tle Cor­re­vio still can't win over FDA pan­el con­cerned with its AFib drug's safe­ty

When the FDA spurned Astellas’ pitch for atrial fibrillation drug vernakalant in 2008, regulators made it abundantly clear that it wasn’t the efficacy they had a problem with — two Phase III trials had shown the drug successfully restored 52% of patients’ heartbeat from irregular to normal — but the cardio safety issues for a drug that was to compete with well established, low-risk options. One licensing deal, one clinical hold and several studies later, the chances of approval aren’t looking any better.