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.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Stephen Hoge, Moderna president (Moderna)

On morn­ing of FDA Covid-19 ad­comm, Mod­er­na com­pletes PhI­II en­roll­ment, putting them neck-and-neck with Pfiz­er

Weeks away from a potential EUA application, Moderna announced they have completed enrollment in their 30,000-person Phase III Covid-19 vaccine trial, with over a third of volunteers non-white and a quarter over the age of 65.

The announcement caps what has been the most closely-watched recruitment race in the history of drug development, as Pfizer and Moderna rushed to get enough volunteers to prove whether or not experimental vaccines could actually protect people from contracting Covid-19. Pfizer reached that mark on Sept. 15. Moderna said around the same time that they would slow down enrollment to ensure they enrolled enough participants from minority and at-risk groups.

Pfiz­er scoops up an an­tibi­ot­ic in rare M&A deal, bag­ging a vir­tu­al start­up op­er­at­ing on a shoe­string bud­get

Pfizer is stepping up with a rare antibiotics buyout deal today, grabbing Palo Alto, CA-based Arixa Pharmaceuticals in a bid to add a new oral version of avibactam, a beta lactamase inhibitor — or BLI — approved back in 2015 as part of the IV treatment Avycaz.

The Arixa acquisition follows some encouraging Phase I responses demonstrating that 60% to 80% of the oral drug is absorbed into the bloodstream. Only 7% of the IV version is absorbed orally, far below the 30% threshold Arixa has pointed to as a therapeutic threshold. The buyout gives Pfizer’s hospital group a line on a new oral combo with antibiotics like ceftibuten to go after drug-resistant cases of urinary tract infections and other ailments.

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News brief­ing: UK biotech 4D phar­ma heads for Nas­daq via SPAC; Dr. Red­dy's shuts down man­u­fac­tur­ing af­ter cy­ber­at­tack

Another pharma company is intending to use a SPAC to join the Nasdaq.

4D pharma, a UK-based biotech, is reverse-merging with a blank check company in a deal worth up to $37.6 million. The move will give 4D pharma a new Nasdaq ticker, which will be $LBPS, using the American Depositary Share program.

As a result of the move, 4D pharma will gain $14.6 million in cash held by the blank check company, dubbed Longevity. The merger is expected to be completed in early 2021, after which shares will be immediately tradeable.

Can B cells break the bound­aries of cell ther­a­py? Long­wood start­up has $52M to prove a new en­gi­neer­ing tech

Back in December 2017, as the cell therapy world was still basking in the virtually back-to-back approvals of two pioneering CAR-Ts, researchers at Seattle Children’s Research Institute reported a scientific first in a different corner of the field: engineer B cells to treat disease.

The team, led by David Rawlings and Richard James, eventually worked with Longwood Fund to start a biotech around those findings. And now Atlas Venture and RA Capital Management are coming on board to lead a $52 million launch round, joined by Alta Partners, for Be Biopharma.

Jason Kelly, Gingko Bioworks CEO (Mike Blake/Reuters via Adobe)

Ex­clu­sive: Eye­ing big Covid-19 test­ing ex­pan­sion, Gink­go rolls out 50M rapid anti­gen di­ag­nos­tics

In what they hope will be a key part of an extensive effort to boost Covid-19 testing in the US, Ginkgo Bioworks is acquiring and distributing 50 million rapid antigen tests that can potentially be used for virus surveillance in schools and communities and for quick, on the ground diagnoses.

The tests, developed by SD Biosensor, are in line with proposals from the Rockefeller Foundation and Harvard epidemiologists, among others, to blanket the country with fast, low-cost tests. Although not yet authorized in the US, they are a key part of testing efforts from the Bill and Melinda Gates Foundation, who announced plans last month to distribute 120 million of them in low and middle income countries. Roche has commercialized the diagnostic in Europe.

Bo Cumbo, AavantiBio CEO (file photo)

Bo Cum­bo jumps from the top com­mer­cial post at Sarep­ta to the helm of a gene ther­a­py start­up with some in­flu­en­tial back­ers, big plans and $107M

After a 7-year stretch building the commercial team at Sarepta, longtime drug salesman Bo Cumbo is jumping to the entrepreneurial side of the business, taking the helm of a startup that’s got several deep-pocket investors. And he’s not just bringing his experience in selling drugs.

He tells me that when he told Sarepta CEO Doug Ingram about it, his boss got excited about the venture and opted to jump in with a $15 million investment from Sarepta to add to the launch money, alongside 3 of the busiest investors in biotech.

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HHS secretary Alex Azar (at the podium) and FDA commissioner Stephen Hahn (Pete Marovich/Getty Images)

Covid-19 roundup: Azar open­ly plan­ning Hahn ouster — re­port; Vul­ner­a­ble pop­u­la­tions like­ly to get vac­cines by Jan­u­ary

The relationship between HHS secretary Alex Azar and FDA commissioner Stephen Hahn has deteriorated to the point where Azar has suggested replacing Hahn, according to a Politico report.

Azar was angered by the FDA’s pushback of the Trump administration’s proposals for authorizing Covid-19 vaccines, so much so that he began openly floating potential replacements for Hahn. The report cited six unnamed sources that said Azar discussed bringing up Hahn’s removal to the White House.

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