Sage plots come­back plan for its ex­per­i­men­tal oral an­ti­de­pres­sant

Tri­als test­ing de­pres­sion drugs in­vari­ably tend to dis­ap­point. Per­haps the most keen­ly-an­tic­i­pat­ed de­pres­sion tri­al of 2019, de­spite great an­a­lyst and in­vestor op­ti­mism, al­so failed in pa­tients with ma­jor de­pres­sive dis­or­der (MDD), evap­o­rat­ing bil­lions from its drug­mak­er Sage Ther­a­peu­tics’ mar­ket val­ue in ear­ly De­cem­ber.

The com­pa­ny — which last spring se­cured the land­mark ap­proval of its in­jectable post­par­tum de­pres­sion drug Zul­res­so — now has an FDA-en­dorsed path for­ward for its ex­per­i­men­tal oral an­ti­de­pres­sant.

The plan is to pur­sue two new in­di­ca­tions for the drug, zu­ra­nolone (or SAGE-217), on the ba­sis of two-week tri­als: post­par­tum de­pres­sion and the acute treat­ment of MDD, in com­bi­na­tion with an ex­ist­ing an­ti­de­pres­sant. These in­di­ca­tions are ex­pect­ed to sup­ple­ment the orig­i­nal plan to get the drug ap­proved for the treat­ment of MDD as an episod­ic ther­a­py.

“Over­all we be­lieve SAGE’s up­dat­ed ‘217 plan makes sense: it of­fers two more in­de­pen­dent shots on goal in MDD and one ad­di­tion­al study in PPD, with­out the need to im­mi­nent­ly raise cash at a dis­tressed val­u­a­tion,” Stifel’s Paul Mat­teis wrote on Wednes­day.

In De­cem­ber, Sage re­port­ed that SAGE-217 had failed to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment over place­bo in the 581-pa­tient late-stage MOUN­TAIN study in pa­tients with MDD. In the tri­al, pa­tients were ei­ther giv­en a 20 mg or 30 mg dose of the drug, or place­bo, once-night­ly for two-weeks.

The hope was the drug would help MDD pa­tients quick­er and more ef­fec­tive­ly than the ex­ist­ing crop of an­ti­de­pres­sants, which can take weeks to kick in. Al­though the 20 mg dose was not ac­tive, the per­for­mance of 30 mg dose was “di­rec­tion­al­ly” pos­i­tive, Sage chief Jeff Jonas had as­sert­ed in an in­ter­view with End­points News.

This da­ta is “like win­ning the sil­ver medal,” Jonas said. “This is not a gi­ant step for mankind we thought we would take, but it is a step in the right di­rec­tion.”

In re­sponse to the MOUN­TAIN fail­ure, Stifel’s Mat­teis had stressed that all hope was not lost for the drug.

“The fail­ure is a sur­prise in one sense, but in an­oth­er sense, not at all un­prece­dent­ed: even Prozac failed in a num­ber of ef­fi­ca­cy stud­ies,” he wrote in a note. “It’s for the lat­ter rea­son that we’re re­luc­tant here to throw in the tow­el on the SAGE bull case that ‘217 still has the po­ten­tial to be­come a block­buster drug.”

Jonas, mean­while, hint­ed that giv­en the 30 mg dose was well tol­er­at­ed, Sage could po­ten­tial­ly en­hance the size of the dose in the oth­er tri­als en­com­pass­ing the larg­er SAGE-217 pro­gram.

The new path for­ward for the drug does ex­act­ly that — the three ad­di­tion­al tri­als will eval­u­ate 50 mg dose of SAGE-217, and are all ex­pect­ed to read­out in 2021.

“Giv­en the state of the world, there’s po­ten­tial­ly some risk to 2021 time­lines (as is the case for all biotech tri­als), how­ev­er, we note that the MOUN­TAIN study on­ly took 8 months to com­plete,” Mat­teis said.

The so-called Rapid Re­sponse Tri­al as­sess­ing co-ini­ti­a­tion of SAGE-217 with a Se­lec­tive Sero­tonin Re­up­take In­hibitor in MDD is es­sen­tial­ly a first-of-its-kind tri­al re­flect­ing the FDA’s re­cent dis­tinc­tion be­tween rapid-act­ing and slow­er-act­ing main­te­nance an­ti­de­pres­sants. “We like this tri­al since it aligns with how we think many psy­chi­a­trists would like to use the drug in the re­al world,” he added.

Sage, which end­ed 2019 with $1 bil­lion in its cof­fers, has con­cerned in­vestors with its spend­ing — last year’s op­er­at­ing ex­pens­es hit $719 mil­lion — as Zul­res­so’s launch has been slow­er than an­tic­i­pat­ed. Spend­ing could be cut for Zul­res­so giv­en the dif­fi­cul­ties of that launch, Mat­teis said.

The Cam­bridge, Mass­a­chu­setts-based com­pa­ny’s shares $SAGE have lost more than 80% of their val­ue since Zul­res­so’s March 2019 ap­proval, clos­ing at $28.80 on Tues­day. The stock was down more than 9% at $26.11 on Wednes­day morn­ing.

“Bot­tom line, the stock looks cheap ($1.5B cap) and we think it just takes some pa­tience, giv­en our view that it isn’t a ques­tion of “if”, but “when” ‘217 be­comes ap­proved for PPD/MDD,” Jef­feries An­drew Tsai said.

So­cial im­age: Jeff Jonas (NBCU Pho­to Bank via Get­ty Im­ages)

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His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

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Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

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No­var­tis re­ports two pa­tient deaths af­ter treat­ment with Zol­gens­ma

Two children with spinal muscular atrophy have died after receiving Novartis’ Zolgensma, a gene therapy designed as a one-time treatment for the rare fatal disease.

The deaths, which resulted from acute liver failure, occurred in Russia and Kazakhstan, Novartis confirmed in a statement to Endpoints News. Having notified health authorities across all the markets where Zolgensma is available, it will update the drug label “to specify that fatal acute liver failure has been reported,” a spokesperson wrote.

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House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

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Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

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J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.

CSL is gathering its four business units under a unified brand identity strategy (Credit: CSL company site)

CSL brings Se­qirus, Vi­for un­der par­ent um­brel­la brand in iden­ti­ty re­vamp

CSL is gathering its brands under the family name umbrella, renaming its vaccine and newly acquired nephrology specialty businesses with the parent initials.

CSL Seqirus and CSL Vifor join CSL Plasma and CSL Behring as the four now uniformly branded business units of the global biopharma. The Seqirus vaccine division was formed in 2015 with the combination of bioCSL and its purchase of Novartis’ flu vaccine business. CSL picked up Vifor Pharma late last year in an $11.7 billion deal for the nephrology, iron deficiency and cardio-renal drug developer.

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