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)

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.

At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

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As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

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Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.