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.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Emer Cooke, EMA director (AP Photo/Geert Vanden Wijngaert)

Ahead of FDA, EMA rec­om­mends au­tho­riz­ing new gene ther­a­py treat­ment for ul­tra-rare dis­ease

Aromatic amino acid decarboxylase (AADC) deficiency is an ultra-rare genetic disease that leaves patients unable to produce certain hormones in the brain, such as dopamine and serotonin, usually leading to developmental delays, weak muscle tone and inability to control the movement of the limbs. It can also lead to multiple organ failure.

To date, there have been no treatments approved for AADC deficiency, which has been identified in less than 150 patients.

Ather­sys tries to post-hoc-an­a­lyze its way out of an­oth­er tri­al fail for stroke stem cell ther­a­py

Athersys’ stem cell therapy has failed yet again.

In a 206-person trial conducted in Japan, Athersys’ stem cell therapy for stroke failed its primary endpoint of “excellent outcome,” a combined measure of three stroke recovery scores.

While a greater percentage of patients in the treatment group reached the primary endpoint compared to placebo, that difference was not statistically significant.

Siddhartha Mukherjee (Brian Ach/Getty Images for The New Yorker)

All Blue's $733M bid to ac­quire Zymeworks turns hos­tile as board bat­tles back — af­ter a biotech celebri­ty jumps in

Yesterday, the team at All Blue Capital — bent on the takeover of a badly battered Zymeworks — brought in celebrated oncologist, Pulitzer prize-winning writer and biotech exec Siddhartha Mukherjee to add some glitz to their proposed board. But they’re still not winning over any converts.

This morning, Zymeworks’ board officially turned this acquisition offer into a hostile showdown, rejecting the unsolicited offer and marshaling its forces to prevent a buyout at $10.50 per share.

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