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.”

Robert Bradway (Photographer: Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Am­gen snaps up can­cer drug play­er Five Prime, adding PhI­II-ready FGFR2b drug in $2B M&A play

Amgen is making a long-awaited move on the M&A side, buying South San Francisco-based Five Prime $FPRX for close to $2 billion and adding a slate of new cancer drugs to the pipeline.

Amgen is paying $38 a share, putting the deal value at $1.9 billion. The stock closed at $21.26 last night, giving investors a 78% premium.

The jewel in the crown of this deal is bemarituzumab, which Amgen describes as a first-in-class, Phase III-ready anti-FGFR2b antibody. Amgen was drawn to the bargaining table by Five Prime’s mid-stage data on gastric cancer, satisfied by PFS and OS data helping to validate FGFR2b as a target. Amgen researchers will now expand on the R&D program in other epithelial cancers, including lung, breast, ovarian and other cancers.

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David Liu (Casey Atkins Photography courtesy Broad Institute)

David Liu has a new big idea: pro­teome edit­ing. It could one day shred tau, RAS and some of the worst dis­ease-caus­ing pro­teins

Before David Liu became famous for inventing new forms of gene editing, he was known around academia in part for a more obscure innovation: a Rube Goldberg-esque system that uses bacteria-infecting viruses to take one protein and turn it into another.

Since 2011, Liu’s lab has used the system, called PACE, to dream up fantastical new proteins: DNA base editors far more powerful than the original; more versatile forms of the gene editor Cas9; insecticides that kill insecticide-resistant bugs; enzymes that slide synthetic amino acids into living organisms. But they struggled throughout to master one of the most common and powerful proteins in the biological world: proteases, a set of Swiss army knife enzymes that cut, cleave or shred other proteins in everything from viruses to humans.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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In the lat­est big in­vest­ment in gene ther­a­py man­u­fac­tur­ing, Bio­gen com­mits $200M to a ma­jor new fa­cil­i­ty in NC

You’d be forgiven for thinking that the only R&D effort of any consequence at Biogen belongs to aducanumab, its controversial Alzheimer’s drug. But behind the uproar around that drug, the big biotech has a full scale pipeline in play that includes a growing focus on developing gene therapies.

Now Biogen plans to build up the kind of manufacturing muscle that will give it an advantage in gaining FDA approvals — where CMC is always key — and then marketing them around the world.

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Lat­est Mass­Bio re­port shows just how much bio­phar­ma's biggest sec­tor boomed in 2020

It’s clear by now that biopharma experienced a massive boom in 2020, but a new report out Thursday says the Massachusetts hub was particularly successful.

The trade group MassBio released its latest industry snapshot, summarizing the last calendar year as the most successful for the Massachusetts biopharma sector. Overall, Massachusetts-based biotechs raised $5.8 billion in 2020, marking a hefty 93% increase from the previous year.

Eli Lil­ly claims a TKO in its long-run­ning ti­tle fight with No­vo Nordisk for the block­buster di­a­betes mar­ket — but there’s a hitch

Eli Lilly isn’t just gunning for a better diabetes drug in tirzepatide. They want to cut ahead of Novo Nordisk’s blockbuster rival Ozempic (semaglutide) on the obesity front as well. But a newly-claimed win in a head-to-head Phase III showdown over reducing A1C while shedding pounds — complete with clear evidence of superiority over the approved rival — could prove a tough sell right now.

Let’s start with the latest data from Lilly.

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Amid back of­fice con­sol­i­da­tion, Gilead ax­es 179 jobs in Cal­i­for­nia

Gilead is chopping 179 jobs in its home state of California as it scales down its headquarters in favor of a hub in North Carolina.

Up to half of the roles would shift to Research Triangle Park, where the company is setting up a new business services and information technology center, the San Francisco Chronicle reported. The precise number will depend on how many employees choose to relocate.

Per a WARN notice filed with the state, the layoffs are expected to be effective May 30.

In­tro­duc­ing End­points FDA+, our new pre­mi­um week­ly reg­u­la­to­ry news re­port led by Zachary Bren­nan

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.