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.”

Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

Tes­la chief Elon Musk teams up with Covid-19 play­er Cure­Vac to build 'R­NA mi­cro­fac­to­ries'

Elon Musk has joined the global tech crusade now underway to revolutionize vaccine manufacturing — now aimed at delivering billions of doses of a new mRNA vaccine to fight Covid-19. And he’s cutting right to the front.

In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

That’s not a lot to go on. But the tweet comes a year after Tesla’s German division in Grohmann and CureVac filed a patent on a “bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing.” CureVac, in the meantime, has discussed a variety of plans to build microfactories that can speed up the whole process for a global supply chain.

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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

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George Yancopoulos (Regeneron)

UP­DAT­ED: Re­gen­eron co-founder George Yan­copou­los of­fers a com­bat­ive de­fense of the po­lice at a high school com­mence­ment. It didn’t go well

Typically, the commencement speech at Yorktown Central School District in Westchester — like most high schools — is an opportunity to encourage students to face the future with confidence and hope. Regeneron president and co-founder George Yancopoulos, though, went a different route.

In a fiery speech, the outspoken billionaire defended the police against the “prejudice and bias against law enforcement” that has erupted around the country in street protests from coast to coast. And for many who attended the commencement, Yancopoulos struck the wrong note at the wrong time, especially when he combatively challenged someone for interrupting his speech with a honk for “another act of cowardness.”

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Vas Narasimhan, Novartis CEO (Patrick Straub/​EPA-EFE/​Shutterstock)

No­var­tis pays $678M for kick­back scheme as Vas Narasimhan tries to dis­tance phar­ma gi­ant from shady be­hav­ior

Novartis has reached another large settlement to resolve misconduct allegations, agreeing to pay more than $678 million to settle claims that it had spent hundreds of millions of dollars on lavish dinners, so-called speaking fees and expensive alcohol “that were nothing more than bribes” to get doctors to prescribe Novartis medications.

The top-shelf alcohol and lavish meals included a $3,250 per person night at Nobu in Dallas, a $672-per person dinner at Washington DC’s Smith & Wollensky and a $314 per person meal at Sushi Roku in Pasadena, according to the Justice Department complaint. There were at least 7 trips to Hooters and fishing trips in Alaska and off the Florida coast. Each of these events were supposed to be “speaker programs” where doctors educated other doctors on a drug, but the DOJ alleged many were “bogus” wine-and-dine events where the drug was barely mentioned, if at all.  (“Nobody presented slides on the fishing trips,” the complaint says.)

No­var­tis los­es biosim­i­lar ap­peal as court up­holds a 31-year mo­nop­oly by Am­gen's En­brel

A new court ruling has strengthened Amgen’s grip on the IP estate around Enbrel, keeping biosimilars of the autoimmune and inflammatory drug at bay until 2029.

Novartis, the patent challenger, isn’t throwing in the towel yet. In a statement noting the failed appeal, its generics division Sandoz noted its reviewing options, “including potential appeal to US Supreme Court.”

It’s been almost four years since the FDA approved Erelzi, Sandoz’s copycat version of Enbrel. While sales of the Pfizer-partnered drug in the US — the market Amgen is in charge of — have dipped slightly during that time, it remains a solid megablockbuster with 2019 revenue slightly above $5 billion.

Sec­ond death trig­gers hold on Astel­las' $3B gene ther­a­py biotech's lead pro­gram, rais­ing fresh con­cerns about AAV

Seven months after Astellas shelled out $3 billion to acquire the gene therapy player Audentes, the biotech company’s lead program has been put on hold following the death of 2 patients taking a high dose of their treatment. And there was another serious adverse event recorded in the study as well, with a total of 3 “older” patients in the study affected.

The incidents are derailing plans to file for a near-term approval, which had been expected right about now.

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An ex­pe­ri­enced biotech is stitched to­geth­er from transpa­cif­ic parts, with 265 staffers and a fo­cus on ‘new bi­ol­o­gy’

Over the past few years, different teams at a pair of US-based biotechs and in labs in Japan have labored to piece together a group of cancer drug programs, sharing a single corporate umbrella with research colleagues in Japan. But now their far-flung operations have been knit together into a single unit, creating a pipeline with 10 cancer drug development programs — going from early-stage right into Phase III — and a host of discovery projects managed by a collective staff of some 265 people.

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New stan­dard of care? FDA hands Pfiz­er, Mer­ck KGaA an OK for Baven­cio in blad­der can­cer

The breakthrough therapy designation Pfizer and Merck KGaA notched for Bavencio in bladder cancer has quickly paved way for a full approval.

The PD-L1 drug is now sanctioned as a first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma, applicable in cases where cancer hasn’t progressed after platinum-containing chemotherapy.

Petros Grivas, the principal investigator of the supporting Phase III JAVELIN Bladder 100, called the approval “one of the most significant advances in the treatment paradigm in this setting in 30 years.”

On a roll, Mer­ck blazes through a new seg­ment of the bio­mark­er trail

Merck has notched an approval for using Keytruda to treat a biomarker-based subset of first-line colorectal cancer patients with unresectable or metastatic tumors, as the pharma giant continues to find new niches for its blockbuster PD-1 star.

The OK is significant in a number of ways. Not only does it build on an accelerated approval for all tumors characterized as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR); it also marks the first single treatment for colorectal cancer that doesn’t contain chemotherapy.