On the heels of a set­back, Sage re­ports PhI­II suc­cess in post­par­tum de­pres­sion -- but ques­tions linger

Two months af­ter get­ting ham­mered on the fail­ure of its lead late-stage study for a rare type of seizures, Sage Ther­a­peu­tics is claim­ing a vic­to­ry in a pair of Phase III stud­ies for the same drug in post­par­tum de­pres­sion.

Sage re­port­ed this morn­ing that both of its late-stage stud­ies for brex­anolone (SAGE-547) for ma­jor post­par­tum de­pres­sion suc­cess­ful­ly edged out a place­bo — but failed to reg­is­ter the big im­prove­ment over a sug­ar pill that was seen in Phase II. And the biotech $SAGE says that it will use the da­ta to back an FDA sub­mis­sion for their drug — which re­quires a 60-hour in­fu­sion — next year.

Sage’s shares spiked in pre-mar­ket trad­ing on Thurs­day and then waf­fled for a but. By mid-day, though, the stock was up 51% as in­vestors bought in­to the up­beat tone.

Jeff Jonas

The biotech re­cruit­ed 226 pa­tients for these two stud­ies for an ail­ment that af­flicts huge num­bers of women each year. Typ­i­cal­ly a dis­ease like PPD would in­volve large num­bers of pa­tients in search of two pos­i­tive out­comes, but Sage be­lieves it’s right on track to break new ground and score a ma­jor OK.

The main goal of both stud­ies was a sig­nif­i­cant re­duc­tion in de­pres­sion scores 60 hours af­ter treat­ment. And on that lev­el the drug scored a 17.7-point mean re­duc­tion for the high dose and a 19.9-point im­prove­ment for the low dose in the first study for se­vere PPD com­pared to 14 points in the place­bo arm. In study two there was a 14.2-point vs 12-point dif­fer­ence in the mod­er­ate PPD group.

In Phase II, re­searchers re­port­ed a 12.2-point spread be­tween the drug and the place­bo, leav­ing Sage de­fend­ing a sig­nif­i­cant­ly re­duced mar­gin of im­prove­ment.

Re­searchers al­so not­ed that the drug ef­fect last­ed through 30 days in the first study, but did not mark a sta­tis­ti­cal­ly sig­nif­i­cant im­pact af­ter a month in the sec­ond study for mod­er­ate PPD, which could raise a red flag on dura­bil­i­ty.

That Phase II com­par­i­son may be a bit of a let­down, con­cedes Leerink’s Paul Mat­teis, but a win in Phase III is a ma­jor plus for Sage, which he be­lieves is head­ed for an ap­proval. Get­ting an oral ver­sion, he adds, would be a tremen­dous boost.

Nonethe­less, the pos­i­tive phase III PPD re­sults are a tech­nol­o­gy val­i­dat­ing event for SAGE who is seek­ing to re­ca­pit­u­late the mech­a­nism of bre­nax­olone in an oral for­mu­la­tion (SAGE-217) across an ar­ray of CNS dis­or­der. In the back­drop of a planned NDA fil­ing for bre­nax­olone, oral da­ta in ma­jor de­pres­sive dis­or­der rep­re­sent the next ma­jor event in 4Q.

There was at least one se­ri­ous ad­verse event as­so­ci­at­ed with the drug, which was not ex­plained in the com­pa­ny’s state­ment. But Sage says the safe­ty pro­file over­all was com­pa­ra­ble to the place­bo arm. More da­ta will be re­leased at an sci­en­tif­ic con­fer­ence.

Sage has mus­tered fierce sup­port as well as plen­ty of crit­ics for its R&D strat­e­gy, us­ing small stud­ies to high­light the po­ten­tial of a drug. And in this case, PPD rep­re­sents the kind of ma­jor mar­ket op­por­tu­ni­ty like­ly to re­quire a sig­nif­i­cant amount of da­ta to win over reg­u­la­tors.

Last Sep­tem­ber the biotech re­port­ed that the drug did no bet­ter than a sug­ar pill in treat­ing su­per-re­frac­to­ry sta­tus epilep­ti­cus.

Now we’ll see how the FDA feels about all of this.

Sage CEO Jeff Jonas tout­ed the re­sults as a game chang­er:

We be­lieve the da­ta rep­re­sent an un­prece­dent­ed op­por­tu­ni­ty in the de­vel­op­ment of treat­ments for PPD, and may serve as the cat­a­lyst for a par­a­digm shift in how the dis­ease is ap­proached and, if ap­proved, may change how PPD is treat­ed.

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.

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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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.

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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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.

UP­DAT­ED: Ob­sE­va makes case for best-in-class hor­mone sup­pres­sive ther­a­py in pos­i­tive uter­ine fi­broid study

About a month after the Swiss biotech disclosed a failed late-stage study in its IVF program, ObsEva on Monday unveiled positive pivotal data on its experimental treatment for heavy menstrual bleeding triggered by uterine fibroids.

ObsEva in-licensed the drug, linzagolix, from Japan’s Kissei Pharmaceutical in 2015. Two doses of the drug (100 mg and 200 mg) were tested against a placebo in the 535-patient Phase III study, dubbed PRIMROSE 2, in patients who were both on and off hormonal add-back therapy (ABT).

Ear­ly-stage can­cer biotech nails $85M C round; Flem­ming Orn­skov's Gal­der­ma scores 'break­through' sta­tus

→ Zentalis Pharmaceuticals just nabbed an $85 million round from a syndicate that includes Matrix Capital, Viking Global Investors, Redmile Group, Farallon Capital, Perceptive Advisors, Surveyor Capital and Eventide Asset Management. Their lead drug is ZN-c5, which is currently in Phase I/II trials. The biotech describes that drug as a “potential best-in-class oral Selective Estrogen Receptor Degrader for estrogen receptor-positive, HER2-negative (ER+/ HER2-) breast cancer.”