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.

Biotech in­vestors and CEOs see two paths to growth, but are they equal­ly vi­able?

The dynamic in the biotech market has been highly volatile in the last few years, from the high peaks immediately after the COVID vaccine in 2021, to the lowest downturns of the last 20 years in 2022. This uncertainty makes calling the exact timing of the market’s turn something of a fool’s errand, according to Dr. Chen Yu, Founder and Managing Partner of TCG Crossover (TCG X). He speaks with RBC’s Noël Brown, Head of US Biotechnology Investment Banking, about the market’s road ahead and two possible paths for growth.

Casey McPherson shows his daughters Rose (left) and Weston around Everlum Bio, a lab that he co-founded to spark a treatment for Rose and others with ultra-rare conditions. (Ilana Panich-Linsman)

Fa­ther starts lab af­ter in­tel­lec­tu­al prop­er­ty is­sues stymie rare dis­ease drug de­vel­op­ment

Under bright lab lights, Casey McPherson holds his 6-year-old daughter, Rose. His free hand directs Rose’s gaze toward a computer screen with potential clues in treating her one-of-a kind genetic condition.

Gray specks on the screen show her cells that scientists reprogrammed with the goal of zeroing in on a custom medicine. McPherson co-founded the lab, Everlum Bio, to spark a treatment for Rose — and others like her. A regarded singer-songwriter, McPherson never imagined going into drug development.

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Fireside chat between Hal Barron and John Carroll, UKBIO19

It’s time we talked about bio­phar­ma — live in Lon­don next week

Zoom can only go so far. And I think at this stage, we’ve all tested the limits of staying in touch — virtually. So I’m particularly happy now that we’ve revved up the travel machine to point myself to London for the first time in several years.

Whatever events we have lined up, we’ve always built in plenty of opportunities for all of us to get together and talk. For London, live, I plan to be right out front, meeting with and chatting with the small crowd of biopharma people we are hosting on October 12 at Silicon Valley Bank’s London headquarters. And there’s a lengthy mixer at the end I’m most looking forward to, with several networking openings between sessions.

Pfizer and BioNTech's original Marvel comic book links evolving Covid vaccine science to Avengers' evolving villain-fighting tools.(Source: Pfizer LinkedIn post)

Pfiz­er, BioN­Tech part­ner with Mar­vel for Avengers and Covid-fight­ing com­ic book

Pfizer and BioNTech are collaborating with Marvel to celebrate “everyday” people getting Covid-19 vaccines in a custom comic book.

In the “Everyday Heroes” digital comic book, an evolving Ultron, one of the Avengers’ leading villains, is defeated by Captain America, Ironman and others. The plotline and history of Ultron is explained by a grandfather who is waiting with his family at a clinic for Covid-19 vaccinations.

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Take­da to pull key hy­poparathy­roidism drug from the mar­ket af­ter years of man­u­fac­tur­ing woes

Takeda on Tuesday morning made an announcement that almost 3,000 people with the rare disease known as hypoparathyroidism were fearing.

Due to unresolved supply issues and manufacturing woes, Takeda said it will cut its losses and discontinue its hypoparathyroidism drug, known as Natpara (parathyroid hormone), halting all manufacturing of the drug by the end of 2024, but the entire inventory will be available until depleted or expired, a company spokesperson said via email.

Eli Lil­ly and Te­va pre­pare for court bat­tle over mi­graine med ri­val­ry

It looks like Eli Lilly and Teva Pharmaceuticals are going to trial.

A federal appeals court on Monday refused to invalidate three of Teva’s patents for its migraine treatment Ajovy, while also declining to issue a summary judgment in favor of either company, which would effectively end the case without a full trial.

Teva filed suit against Lilly back in 2018, alleging that the company infringed upon nine patents with its rival migraine drug Emgality. The rival drugs were both approved in September 2018 for the preventative treatment of migraine, and are designed to block calcitonin gene-related peptide (CGRP), a protein associated with the onset of migraine pain.

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Kaile Zagger, Infinant Health CEO

UC Davis mi­cro­bio­me spin­out re­brands in­fant sup­ple­ment busi­ness with na­ture fo­cus

When Kaile Zagger took the helm of UC Davis spinout Evolve Biosystems several months ago, the company billed itself as a probiotic maker.

However, she believes the company’s Evivo supplement designed to help infants develop a healthy gut microbiome is “so much more” — and that, she said, calls for a rebrand.

Evolve has, well, evolved into Infinant Health, the company announced on Monday. The new name is a mash-up of the words “infant” and “infinite,” representing the company’s goal of expanding beyond infant care. While its sole product, Evivo, is intended for newborns, Infinant is “quickly developing” an option for kids through the age of two.

FDA+ roundup: Ad­comm date set for Cy­to­ki­net­ics heart drug; New gener­ic drug guid­ance to re­duce fa­cil­i­ty de­lays

The FDA on Wednesday set Dec. 13 as the day that its Cardiovascular and Renal Drugs Advisory Committee will review Cytokinetics’ potential heart drug, meaning regulators aren’t likely to meet the Nov. 30 PDUFA date that was previously set.

The drug, known as omecamtiv mecarbil, read out its first Phase III in November 2020, hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as the key to breaking into the market, failing to significantly differ in reducing cardiovascular death from placebo.

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Bob Azelby, Eliem Therapeutics CEO

Eliem says ear­li­er drug ex­po­sure is­sues have been re­solved, drops one epilep­sy in­di­ca­tion

After being forced to delay two Phase IIa trials and blaming CMC issues on a Phase Ib miss, Eliem Therapeutics believes it’s now in the clear.

The Seattle and UK-based biotech put out word Wednesday morning about how it conducted new early-stage studies to confirm why low exposure issues arose during the Phase Ib. After researchers compared the results of the studies, Eliem found “no meaningful difference” between them and ruled out CMC as the reason for the foiled Phase Ib study, the company said in a press release.