FDA ap­proves trail­blaz­ing post­par­tum de­pres­sion ther­a­py, in cru­cial mile­stone for wom­en's health

In a land­mark de­ci­sion, the US health reg­u­la­tor has ap­proved the first treat­ment for moth­ers suf­fer­ing from post­par­tum de­pres­sion (PPD), a com­mon but of­ten over­looked and stig­ma­tized com­pli­ca­tion of child­birth that af­fects an es­ti­mat­ed 1 in 7 women.

The man­u­fac­tur­er of the in­jectable treat­ment — Sage Ther­a­peu­tics $SAGE — has been busy, rais­ing more than half a bil­lion dol­lars through the sale of its stock to sup­port the com­mer­cial roll­out of the drug, hir­ing a 180-strong sales­force and set­ting up se­lect cen­ters for women to get ad­min­is­tered with the one-time treat­ment un­der med­ical su­per­vi­sion.

The drug brex­anolone — to be sold as Zul­res­so — was orig­i­nal­ly de­signed for at-home in­fu­sions. But that ex­pec­ta­tion was scut­tled last year, af­ter the agency and ex­perts un­der­scored con­cerns about faint­ing episodes, which oc­curred in 6 of 140 women ex­posed to brex­anolone dur­ing in­fu­sion. Still, the drug won a ring­ing en­dorse­ment by the FDA ad­vi­so­ry pan­el on the ba­sis that des­ig­nat­ed fa­cil­i­ties to mon­i­tor ad­min­is­tra­tion (en­com­pass­ing a 12-hour fol­low-up to the 60-hour in­fu­sion) would be set up. Sage ac­com­mo­dat­ed this de­mand by sub­mit­ting a fresh risk eval­u­a­tion and mit­i­ga­tion strate­gies (REMS) plan, which pushed the FDA de­ci­sion date by three months to March 19.

Mike Cloo­nan

The treat­ment — which car­ries a boxed warn­ing high­light­ing the risk of sud­den loss of con­scious­ness — is ex­pect­ed to launch in late June, af­ter the DEA sched­ules the drug, con­sis­tent with oth­er ap­proved GABAer­gic ther­a­pies — agents that di­rect­ly mod­u­late the GA­BA sys­tem in the body or the brain.

Sage has as­signed a list price of $7,450 per Zul­res­so vial, re­sult­ing in a pro­ject­ed av­er­age course of ther­a­py cost of $34,000 per pa­tient be­fore dis­counts, a com­pa­ny spokesper­son said on Tues­day.

The drug de­vel­op­er has been con­sult­ing with “hun­dreds of pay­ers” to se­cure ac­cess, Sage’s chief busi­ness of­fi­cer Mike Cloo­nan said in an in­ter­view with End­points News ahead of the de­ci­sion.

In dis­cus­sions with phar­ma­cy ben­e­fit man­agers, the com­pa­ny feels “com­fort­able that we won’t have to re­bate a sig­nif­i­cant por­tion here, be­cause of the in­no­va­tion here we’re build­ing with Zul­res­so,” he said.

As part of its REMS strat­e­gy, the com­pa­ny is al­so work­ing on es­tab­lish­ing des­ig­nat­ed cen­ters where women can ac­cess the ther­a­py un­der med­ical su­per­vi­sion, Cloo­nan added, not­ing that “it can take months to get a site cer­ti­fied, reg­is­tered, and to es­tab­lish re­im­burse­ment path­ways.”

PPD is con­sid­ered a life-threat­en­ing con­di­tion be­cause pa­tients car­ry a risk of sui­cide, but aware­ness of the dis­or­der is patchy com­pared to oth­er ma­jor de­pres­sive con­di­tions, part­ly due to the so­cial stig­ma of be­ing la­beled an “un­hap­py moth­er” — an is­sue a grow­ing num­ber of celebri­ty moth­ers such as mod­el and cook­book au­thor Chris­sy Teigen have brought in­to the cul­tur­al zeit­geist.

PPD, which is an um­brel­la term for sev­er­al mood dis­or­ders, has pro­found neg­a­tive ef­fects on the ma­ter­nal-in­fant bond and lat­er in­fant de­vel­op­ment. Al­though a num­ber of an­ti­de­pres­sants ex­ist in the mar­ket, there is lit­tle ev­i­dence of their ef­fi­ca­cy in PPD, they usu­al­ly take 6 to 8 weeks to kick in and none are specif­i­cal­ly ap­proved for PPD.

Ac­cord­ing to Sage, rough­ly 400,000 women in the Unit­ed States suf­fer from PPD any giv­en year, al­though on­ly about half are di­ag­nosed. With Zul­res­so, the com­pa­ny ini­tial­ly plans to tar­get the se­vere PPD pop­u­la­tion, rep­re­sent­ed by about 20-30% of those 200,000 iden­ti­fied pa­tients.

Since pa­tients must be con­tin­u­ous­ly mon­i­tored by a health­care pro­fes­sion­al and ac­com­pa­nied dur­ing in­ter­ac­tions with their chil­dren when be­ing in­fused with the ther­a­py, Stifel an­a­lyst Paul Mat­teis’ fore­cast was com­par­a­tive­ly mod­est. He pro­ject­ed about $270 mil­lion in peak US sales in 2023, based on 10% pen­e­tra­tion in the se­vere PPD set­ting, with no use in mod­er­ate/mild pa­tients.

Mean­while, the com­pa­ny’s keen­ly watched oral PPD ther­a­py — SAGE-217 — is the one with big tick­et block­buster po­ten­tial, hav­ing re­cent­ly cleared a Phase III study with fly­ing col­ors. The pill — al­so be­ing eval­u­at­ed for ma­jor de­pres­sive dis­or­der (MDD) and oth­er mood dis­or­ders — ap­pears to be an im­prove­ment over brex­anolone as it is not prone to in­duc­ing the loss of con­scious­ness side ef­fect seen with the use of the in­jectable. Sage in­tends to wait for da­ta from a piv­otal study on the pill in pa­tients with ma­jor de­pres­sive dis­or­der (ex­pect­ed in 2020) be­fore sub­mit­ting a mar­ket­ing ap­pli­ca­tion.

Sage’s main ri­val is Mar­i­nus $MRNS, whose drug ganax­olone is al­so un­der eval­u­a­tion for PPD. An IV for­mu­la­tion of ganax­olone is cur­rent­ly in a Phase II study in se­vere PPD pa­tients, while mid-stage da­ta from an oral for­mu­la­tion of ganax­olone in mod­er­ate PPD pa­tients are ex­pect­ed in the first half of this year.

Zul­res­sa’s ap­proval bodes well for Mar­i­nus $MRNS, ar­gued Jef­feries’ An­drew Tsai in a re­cent note. “We think ap­proval would have a neu­tral im­pact on Mar­i­nus, de­spite Sage be­ing 2-3 years ahead, giv­en: 1) FDA ap­proval should de-risk the class/mech­a­nism broad­ly, and 2) the FDA has re­quired Sage to in­tro­duce a REMS pro­gram that lim­its its use case to a cer­ti­fied health­care fa­cil­i­ty (e.g. hos­pi­tal), which may open up an op­por­tu­ni­ty for Mar­i­nus. Sage‘s next-gen oral drug (SAGE-217) has al­so shown com­pelling ef­fi­ca­cy in Phase II/III PPD and MDD stud­ies and so far does not cause faint­ing (syn­cope) or loss of con­scious­ness (e.g. al­low­ing for home use), but our base case as­sump­tion is for the play­ers to share parts of the PPD mar­kets.”

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive PhI­II for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma. 

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

UP­DAT­ED: As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.