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.”

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Psilocybin mushrooms (via The Denver Post)

In a key step for psy­che­del­ic re­search, mag­ic mush­room com­pound clears first clin­i­cal safe­ty hur­dle

Exasperated with the often-ineffective existing slate of antidepressants, COMPASS Pathways set up shop in London 2016 — and made a beeline for psilocybin, the psychoactive ingredient in magic mushrooms.

On Wednesday, the startup said its man-made version of the chemical — which is illegal across geographies in its natural fungi form — had been well-tolerated in an early-stage, placebo-controlled trial in 89 healthy volunteers.

Al­pham­ab On­col­o­gy rounds out HKEX's sec­ond biotech IPO year with $230M raise and high lo­cal in­ter­est

Alphamab Oncology has inspired a surge of local interest in what will likely be the Hong Kong Stock Exchange’s last biotech run of the year, pricing its IPO on the high end of the range and raising over $230 million (HK$1.83 billion).

After rejigging the offering structure and making up to 50% available for enthusiastic local investors, the biotech sold 179.4 million shares at $1.31 (HK$10.2) and saw its stock rise to $1.77 ($13.8) on the first day of trading.

For sale: Long-act­ing PhI­II GLP-1 di­a­betes drug that’s way be­hind ri­vals, now spurned by Sanofi

Almost exactly 4 years ago Sanofi came to the bargaining table with South Korea’s Hanmi bearing $434 million dollars in cash and offering about $4 billion in milestones to in-license their once-weekly GLP-1 injectable. The pact was intended to revive their ailing diabetes division. Instead, it turned into a very expensive grave to mark the end of Sanofi’s R&D ambitions in the field.

Sanofi CEO Paul Hudson used efpeglenatide’s demise — while committing to paying hundreds of millions of more dollars to push it through 5 late-stage studies — as a marker of the company’s determination to stay focused on first and best-in-class drugs.

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Parkin­son's trans­plants emerge as stem cell pi­o­neer Jeanne Lor­ing joins R&D race

Jeanne Loring hadn’t studied Parkinson’s in 22 years when she got an email from a local neurologist.

The neurologist, Melissa Houser, didn’t know Loring had ever published on the disease. She was just looking for a stem cell researcher who might hear her out. 

“I think I was just picked out a hat,” Loring told Endpoints News. 

At a meeting in Loring’s Scripps Research office, Houser and a Parkinson’s nurse practitioner, Sherrie Gould, asked her why there was so much research done in stem cell transplants for other neurodegenerative diseases but not Parkinson’s. They wanted to know if she would work on one. 

What does $6.9B buy these days in on­col­o­gy R&D? As­traZeneca has a land­mark an­swer

Given the way the FDA has been whisking through new drug approvals months ahead of their PDUFA date, AstraZeneca and their partners Daiichi Sankyo may not have to wait until Q2 of next year to get a green light on trastuzumab deruxtecan (DS-8201).

The pharma giant this morning played their ace in the hole, showing off why they were willing to commit to a $6.9 billion deal — with $1.35 billion in a cash upfront — to partner on the drug.

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Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

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Large advertisements for the drug Vivitrol decorate the walls of Grand Central Station on June 15, 2017 in New York City. (Photo: Andrew Lichtenstein via Getty)

FDA slaps down Alk­er­mes for mis­lead­ing Viv­it­rol ads — don't for­get vul­ner­a­bil­i­ty to opi­oid over­dose

The ads piqued interest as soon as they started appearing in 2016: at Grand Central Station, on the Red Line in Cambridge, and on a billboard off the New Jersey Turnpike. All showed a young person, generally with his or her arms crossed, and the question, “what is Vivitrol?”

Vivitrol’s maker, Alkermes, was in the midst of a marketing and lobbying campaign to promote the anti-opioid addiction drug — a campaign that would face significant backlash for tarnishing competitors despite little evidence for Vivitrol’s superiority.

FDA in-house re­view spot­lights an is­sue with one of Hori­zon's end­points but notes ef­fi­ca­cy for lead drug

The FDA in-house review highlights a disagreement of investigators’ use of a key endpoint by Horizon Pharma in the late-stage trial for the top drug in its pipeline, but largely agreed that the antibody was effective.

Horizon submitted a BLA for thyroid eye disease (TED) drug teprotumumab in March, less than two years after they bought the drug (and the rest of a division) from Narrow River for $145 million upfront. With breakthrough status, priority review, orphan designation and in-house sales projections of up to $750 million, the one-time Roche reject became the marquee pipeline asset for a company that’s developed some of the world’s most expensive drugs.