The FDA just signed off on a For­mu­la 1 piv­otal track for Sage's post­par­tum de­pres­sion drug

Jeff Jonas, Sage

Sage Ther­a­peu­tics says the FDA has signed off on an as­ton­ish­ing­ly short clin­i­cal de­vel­op­ment path­way for post­par­tum de­pres­sion which may al­low for an ap­proval af­ter a pair of tiny Phase II stud­ies which are al­ready un­der­way.

These two mid-stage stud­ies — 202B and 202C — will read out in the sec­ond half of next year. And Cam­bridge, MA-based Sage says that the min­utes of its FDA meet­ing make clear that the biotech on­ly needs to make a few small ad­just­ments, in­clud­ing an in­crease in sam­ple size, to make these stud­ies reg­is­tra­tional.

If suc­cess­ful, Sage would be on track to seek out an ap­proval in 2018. And its shares jumped 8% on the news.

Ac­cord­ing to clin­i­cal­tri­, the two Phase II stud­ies com­bined were set to en­roll few­er than 100 pa­tients — the kind of tri­al size you might ex­pect to see for a very rare dis­ease. The biotech is look­ing to build on some ex­cite­ment trig­gered by their first tiny study.

In an email to End­points News, CEO Jeff Jonas says that tran­si­tion­ing to a piv­otal ef­fort will re­quire about 200 pa­tients in both stud­ies. And the biotech is al­so open­ing up sites in the EU. But Jonas cau­tions against read­ing too much in­to pos­si­ble im­pli­ca­tions for oth­er biotechs.

Jonas writes:

We de­signed the ear­li­er pro­grams in the hopes of achiev­ing this ex­pe­dit­ed re­view.  We felt that many fac­tors jus­ti­fied an ef­fi­cient de­vel­op­ment strat­e­gy.  In brief, re­call that SAGE-547 is based on a nat­u­ral­ly oc­cur­ring com­pound, has had a re­as­sur­ing safe­ty pro­file with a cou­ple hun­dred pa­tients ex­posed to the drug across mul­ti­ple set­tings, has a short half-life, and is ad­min­is­tered on­ly over 60 hours in a med­ical set­ting for PPD.  So we view this (as) a de­ci­sion specif­i­cal­ly based on the da­ta pack­age avail­able re­gard­ing SAGE-547.

The green light, though, comes at a time that the FDA is at­tract­ing in­creas­ing com­ment for its will­ing­ness to fun­da­men­tal­ly rewrite the rules on drug de­vel­op­ment in fa­vor of the de­vel­op­ers. As a “break­through” ther­a­py, SAGE-547 is ex­pect­ed to get quick han­dling at the FDA. But reg­u­la­tors have main­tained a high bar on stud­ies re­lat­ed to de­pres­sion, where the place­bo ef­fect has fre­quent­ly scut­tled clin­i­cal tri­al ef­forts.

By its own count, Sage is shoot­ing at a dis­ease pop­u­la­tion of 500,00 to 750,000 women in the US alone who suf­fer from PPD each year.

Paul Mat­teis at Leerink looked at the im­pli­ca­tions for Sage:

We as­sumed a (very) late 2019 launch pre­vi­ous­ly – with just $3MM in 2019E PPD sales – thus, the up­dat­ed guid­ance, in­clud­ing a 2018E NDA, may move sales a full year ahead. SAGE not­ed that “oth­er mi­nor mod­i­fi­ca­tions” have been asked by the FDA, but most im­por­tant­ly, the clin­i­cal end­points of the study – which are stan­dard in de­pres­sion – re­main the same. SAGE al­so be­lieves it does not need to ini­ti­ate any oth­er stud­ies be­yond those that are cur­rent­ly un­der­way; ad­di­tion­al safe­ty da­ta can be ob­tained through open-la­bel tri­als. Re­call that the PPD pro­gram as it was pre­vi­ous­ly out­lined to­taled two stud­ies (to­tal N = ~100) across se­vere and mod­er­ate PPD. For reg­is­tra­tion, we had been cau­tious that a larg­er safe­ty data­base – and pos­si­bly oth­er stud­ies – might be re­quired giv­en the lack of reg­u­la­to­ry prece­dent in PPD. And while SAGE did not dis­closed the fi­nal­ized (larg­er N), the abil­i­ty to still gen­er­ate top-line da­ta in 2H17 rep­re­sents a pos­i­tive on tim­ing, and the to­tal­i­ty of the an­nounce­ment is pos­i­tive on con­vey­ing a clear de­vel­op­ment path for­ward.

Sage, though, has at­tract­ed plen­ty of short in­ter­est along the way as it hus­tled from tiny proof-of-con­cept stud­ies to reg­is­tra­tional stud­ies for SAGE-547.

Sahm Ad­ran­gi’s Ker­ris­dale Cap­i­tal has sin­gled out Sage Ther­a­peu­tics $SAGE as a big biotech short sell­er play, lay­ing out a de­tailed ar­gu­ment aimed at stok­ing doubt in the biotech’s rare dis­ease drug while try­ing to slash the com­pa­ny’s stock price. The Wall Street hedge fund is­sued a 28-page re­port last spring as­sert­ing that SAGE-547 — al­so de­signed to treat rare cas­es of pro­tract­ed seizures called su­per-re­frac­to­ry sta­tus epilep­tics — is es­sen­tial­ly doomed, like­ly poised to fail the on­go­ing Phase III study or come up far short on a mar­ket that’s much small­er than the de­vel­op­er has as­sert­ed.

In its last PPD study, Sage said that the drug–aimed at GABAA re­cep­tors in the brain–hit the pri­ma­ry end­point in the Phase II, which in­volved on­ly 21 pa­tients; and on­ly a few pa­tients ac­tu­al­ly got the drug. In­ves­ti­ga­tors tracked a 60% re­mis­sion rate at 60 hours with a 30-day fol­low-up.

Re­mis­sion, Sage re­port­ed, as de­ter­mined by a HAM-D ≤7, mea­sured at 60 hours, was seen in 7 of 10 of the SAGE-547 group com­pared with 1 of 11 in the place­bo group (p=0.008). Sim­i­lar­ly, at 30 days, 7 of 10 of the SAGE-547 group and 2 of 11 in the place­bo group were in re­mis­sion (p=0.03).

“We are en­cour­aged by the FDA’s feed­back and ap­pre­ci­ate their guid­ance re­gard­ing our SAGE-547 de­vel­op­ment pro­gram in post­par­tum de­pres­sion,” said Sage CEO Jeff Jonas. “Based on our meet­ing, we have clear and ef­fi­cient di­rec­tion for the ex­pe­dit­ed de­vel­op­ment path for­ward for SAGE-547 to po­ten­tial­ly sup­port a New Drug Ap­pli­ca­tion (NDA) in 2018.”

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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Chris Garabedian. Xontogeny

Per­cep­tive teams up with Chris Garabe­di­an to open up a new, $210M biotech fund fo­cused on A rounds

Perceptive Advisors is one of those prolific biotech investor groups which has traditionally enjoyed zeroing in on clinical-stage investments and crossover rounds, a group that prefers more established drug development players with near-term payoff potential.

But now they’re partnering with Xontogeny chief and longtime biotech entrepreneur Chris Garabedian on a $210 million fund — with money contributed by institutional investors and family funds — to go into the launch space with their first early-stage VC fund. Dubbed the Perceptive Xontogeny Venture Fund, LP, or just PXV Fund, they plan to favor upstarts that Garabedian is fostering in his incubator. But they’ll also plan to reach outside that inner circle for more A rounds to back, with plans to dominate initial funding with $10 million to $20 million per newborn biotech.

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.”

This is the second biotech buyout pact today, marking a brisk tempo of M&A deals in the lead-up to the big JP Morgan gathering in mid-January. It’s no surprise the acquisitions are both for cancer drugs, where Sanofi will try to make its mark while Merck beefs up a stellar oncology franchise. And bolt-ons are all the rage at the major pharma players, which you could also see in Novartis’ recent $9.7 billion MedCo buyout.

ArQule — which comes out on top after their original lead drug foundered in Phase III — highlighted early data on ‘531 at EHA from a group of 6 chronic lymphocytic leukemia patients who got the 65 mg dose. Four of them experienced a partial response — a big advance for a company that failed with earlier attempts.

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US biosim­i­lar launch­es about to turn a cor­ner

The US biosimilar industry has lingered in the shadow of the European market since the US pathway for approvals was initiated in 2009.

Ten years later (or less than five years since the first FDA approval of a biosimilar), and just 42% (11 out of 26) of FDA-approved biosimilars have launched. But in the next three months (see chart below), a clutch of new biosimilars will hit the market, including new ones in oncology, hinting at a wave of uptake.

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.