Sage’s quick flip in­to PhI­II crash­es as lead drug fails bad­ly for rare type of seizures

Af­ter build­ing in­tense in­ter­est in its lead drug for su­per-re­frac­to­ry sta­tus epilep­ti­cus with da­ta from tiny stud­ies, Sage Ther­a­peu­tics $SAGE says the drug failed bad­ly in Phase III.

Com­par­ing brex­anolone (SAGE-547) with a place­bo, the drug act­ed just like a sug­ar pill, with a 43.9% re­sponse for the drug com­pared to 42.4% in the place­bo arm — and a mis­er­able p-val­ue of 0.8775.

Sage’s shares dropped more than 20% on the news. But by the af­ter­noon the biotech had trimmed its loss­es, with the stock down about 14% — a mod­est re­treat giv­en the bad judg­ment this biotech has shown.

Jeff Jonas, Sage

Sage cre­at­ed both fierce be­liev­ers as well as even fiercer crit­ics of its drug for rare cas­es of pro­tract­ed seizures as CEO Jeff Jonas con­fi­dent­ly pre­dict­ed suc­cess. More than a year ago Sahm Ad­ran­gi’s Ker­ris­dale Cap­i­tal ex­e­cut­ed a short at­tack on Sage, caus­ti­cal­ly sum­ma­riz­ing its move from a small Phase I/II to a piv­otal tri­al as a strat­e­gy doomed to fail­ure.

Ker­ris­dale’s re­port picked apart da­ta from a sin­gle-arm study with no com­par­i­son group of pa­tients, which they be­lieve set the stage for the biotech to claim a big win with­out ac­tu­al­ly putting the ther­a­py to the test. And they add that there are ex­ist­ing ther­a­pies that go af­ter the ex­act same tar­get with sim­i­lar out­comes.

The fail­ure here will al­so cast a cloud over Sage’s oth­er R&D work, in­clud­ing a new drug for post­par­tum de­pres­sion which was al­so tout­ed with small stud­ies il­lus­trat­ing pos­i­tive re­sults.

But not every­one thinks the ug­ly flop here reads through to the rest of the pipeline. Notes Paul Mat­teis at Leerink:

The in­vest­ment de­bate this morn­ing cen­ters around the de­gree to which SRSE reads neg­a­tive­ly on­to the clin­i­cal po­ten­tial of SAGE-547 in PPD (and by ex­ten­sion oth­er mood dis­or­ders); while we un­der­stand that the lack of sig­nal in SRSE has ren­dered some in­vestors more cau­tious in their in­ter­pre­ta­tion of SAGE‘s many small CNS da­ta sets, for us, it’s hard to see a tan­gi­ble readthrough on­to PPD, which has (1) place­bo-con­trolled da­ta, (2) bet­ter un­der­stood nat­ur­al his­to­ry/place­bo ef­fects, and (3) break­through ther­a­py des­ig­na­tion.

As for Jonas, he still found rea­sons to ap­plaud the work.

“I’m proud of the Sage team for the sig­nif­i­cant progress they have made in im­prov­ing our un­der­stand­ing of how to best treat these crit­i­cal­ly ill pa­tients,” he said. “SRSE is a com­pli­cat­ed con­di­tion that is poor­ly un­der­stood, and I want to thank the pa­tients, their fam­i­lies, and the in­ves­ti­ga­tors who par­tic­i­pat­ed in the STA­TUS Tri­al. Al­though we did not meet the pri­ma­ry end­point, this first-ever tri­al in a high­ly vari­able and com­plex pa­tient pop­u­la­tion con­firms that re­search in a crit­i­cal care unit is pos­si­ble and deep­ens our un­der­stand­ing of GA­BA mech­a­nisms and their ef­fect on brain cir­cuit­ry. As we con­tin­ue ex­am­in­ing da­ta from the STA­TUS Tri­al in the com­ing weeks, I’m hope­ful this in­for­ma­tion will in­form cur­rent treat­ments, and aid in the de­vel­op­ment of fu­ture treat­ments for pa­tients with SRSE.”

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

(Image: Associated Press)

Amarin emerges from an ex­pert pan­el re­view with a clear en­dorse­ment for Vas­cepa and high odds of suc­cess when the FDA weighs in for­mal­ly

Several FDA experts who gathered Thursday to consider the landmark approval of Vascepa to reduce cardio events in an at-risk population voiced their unease about various aspects of the efficacy and safety data, or ultimately the population it should be used to treat. But the overwhelming belief that the data pointed to the drug’s benefit and clearly outweighed risks carried the day for Amarin.

The panel voted unanimously (16 to 0) to support the company’s positive data presentation — backing an OK for expanding the label to include reducing cardio risk. The vote points Amarin $AMRN down a short path to a formal decision by the FDA, with the odds heavily in its favor. Chances are the rest of the questions about the future of this drug will be hashed out in the label’s small print.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,500+ biopharma pros reading Endpoints daily — and it's free.

What does $62B buy you these days? A lot, says Take­da ex­ecs as the phar­ma play­er promis­es a block­buster R&D fu­ture

First comes the $62 billion buyout. Then comes the asset auction and reorganization to pay down debt. Now comes the detailed pledge of a bigger, brighter future in drug development.

That’s where Takeda finds itself on R&D day today, about 11 months after closing on their Shire acquisition. R&D chief Andy Plump is joining CEO Christophe Weber and other top members of the team to outline a new set of priorities in the greatly expanded pipeline at Takeda, which has jumped into the top ranks of the world’s pharma giants in the wake of the Shire deal.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,500+ biopharma pros reading Endpoints daily — and it's free.

BeiGene CEO John Oyler at an Endpoints event in Shanghai, October 2018 (Credit: Endpoints News/PharmCube)

UP­DAT­ED: Chi­na's BeiGene scores first-ever FDA ap­proval — but can they carve up J&J's block­buster fran­chise?

Weeks after Amgen took a $2.7 billion stake in BeiGene, the Beijing-based biotech has secured its first-ever FDA approval for zanubrutinib, a BTK inhibitor, months ahead of schedule.

BeiGene’s drug, branded as Brukinsa, has secured accelerated approval for adult patients with mantle cell lymphoma (MCL) — a typically aggressive, rare, form of blood cancer — who have received at least one prior therapy.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,500+ biopharma pros reading Endpoints daily — and it's free.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,500+ biopharma pros reading Endpoints daily — and it's free.

GSK's asth­ma bi­o­log­ic Nu­cala scores in rare blood dis­or­der study

GlaxoSmithKline’s asthma drug Nucala, which received a resounding FDA rejection for use in chronic obstructive pulmonary disease (COPD) last year, has shown promise in a rare blood disorder.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,500+ biopharma pros reading Endpoints daily — and it's free.

Mer­ck buys a fledg­ling neu­rode­gen­er­a­tive biotech spawned by an old GSK dis­cov­ery al­liance. What’s up with that?

Avalon Ventures chief Jay Lichter has a well-known yen for drug development programs picked up in academia. And what he found in Haoxing Xu’s lab at the University of Michigan pricked his interest enough to launch one of his umbrella biotechs in San Diego.

Xu’s work laid the foundation for Avalon to launch Calporta, which has been working on finding small molecule agonists of TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) for lysosomal storage disorders. And that pathway, they believe, points to new approaches on major market neurodegenerative diseases like Parkinson’s, ALS and Alzheimer’s.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,500+ biopharma pros reading Endpoints daily — and it's free.

Carson Block. Muddy Waters via YouTube

Shorts ga­lore: Mud­dy Wa­ters sees slide for Pep­tiDream, tweets con­cerns about Fi­bro­Gen's new da­ta

The short seller Muddy Waters is taking aim at Japan’s most profitable biotech, projecting a slide for a company that has skyrocketed over the last four years. Meanwhile, the firm tweeted out an analysis accusing FibroGen of manipulating data to obscure safety concerns in their latest reveal, although some investors seem satisfied by the biotech’s explanation.

Muddy Waters shorted PeptiDream, a Japanese biotech-for-hire that leveraged its peptide library into partnerships with some of the world’s largest pharmaceutical companies, a 50% profit margin and $6 billion valuation. The firm noted that despite its esteem, PeptiDream has failed to bring a drug to market 13 years after its 2006 launch (although this is not especially rare for biotech).

Pin­cer move­ment: Cal­i­for­nia biotech gets $35M to suf­fo­cate can­cer in co­or­di­nat­ed at­tack

Having served in Afghanistan, the navy veteran leading California-based EpicentRx wants to leave no patient behind with his arsenal of anti-cancer drugs. On Thursday, the company was given a $35 million boost to further its mission.

The injection of funds will be used to shepherd its late-stage CD47 drug, RRx-001, to the FDA for marketing, and its oncolytic virus program into the clinic.

RRx-001, engineered as an agent that makes tumor cells more sensitive to therapy, is in a Phase III trial in combination with chemotherapy for use in third-line and beyond small cell lung cancer (SCLC). The drug has been granted orphan drug designation from FDA for SCLC, neuroendocrine cancer and glioblastoma.