Safe­ty con­cerns lead to a split FDA pan­el vote on Sanofi/Lex­i­con di­a­betes drug

The first po­ten­tial pill for pa­tients with the less com­mon type 1 di­a­betes, who pro­duce no in­sulin, was the sub­ject of an atyp­i­cal hung ju­ry vote at an FDA pan­el on Thurs­day, in which ex­perts were di­vid­ed even­ly over whether the life-threat­en­ing risk of di­a­bet­ic ke­toaci­do­sis as­so­ci­at­ed with the drug off­set its ben­e­fit.

The drug, so­tagliflozin, from Lex­i­con Phar­ma and Sanofi is be­ing de­vel­oped for both type I and type II di­a­betes. It is de­signed to in­hib­it two pro­teins in­volved in glu­cose reg­u­la­tion: SGLT1, which is re­spon­si­ble for glu­cose re­ab­sorp­tion in the GI tract and SGLT2, which is re­spon­si­ble for glu­cose re­ab­sorp­tion by the kid­ney.  Many ex­ist­ing di­a­betes drugs on­ly tar­get SGLT2. Al­though the mol­e­cule is cur­rent­ly be­ing test­ed in a pletho­ra of tri­als in pa­tients with type II di­a­betes, the oral drug is cur­rent­ly un­der FDA re­view for type 1 di­a­bet­ics, who face mul­ti­ple dai­ly in­jec­tions of in­sulin, or use an in­sulin pump, to achieve glycemic con­trol.

The ap­pli­ca­tion for type 1 di­a­bet­ics was on the ba­sis of three late-stage tri­als. How­ev­er, an in­crease in the risk of di­a­bet­ic ke­toaci­do­sis (DKA) was ob­served with so­tagliflozin treat­ment — and it was this is­sue that was cen­tral to the split 8-8 vote on Thurs­day. Al­though the FDA is not ob­lig­at­ed to fol­low the rec­om­men­da­tions of the pan­el, it usu­al­ly does. In this case, the reg­u­la­tor has re­ceived a de­cid­ed­ly mixed mes­sage, and is set to make its de­ci­sion by March 22. The drug is al­so un­der EMA re­view.

In a re­port pub­lished on Tues­day, FDA re­view­ers ac­knowl­edged that the risk of DKA has been ob­served with SGLT2 in­hibitor use in type II di­a­bet­ics, and ex­ist­ing ap­proved drugs in the class car­ry warn­ings to high­light the risk. “While all pa­tients with type 1 di­a­betes may to some de­gree be at risk for DKA, so­tagliflozin ther­a­py clear­ly in­creas­es that risk, and the risk may be un­pre­dictable,” reg­u­la­to­ry staff wrote.

In the meet­ing of in­de­pen­dent ex­perts on Thurs­day, near­ly all pan­elists, re­gard­less of their fi­nal vote, agreed the drug — to be sold as Zyn­quista — would on­ly be ap­pro­pri­ate for a small sub­set of par­tic­u­lar­ly at­ten­tive type I di­a­betes pa­tients, in con­text of the DKA risk.

Stifel’s Stephen Wil­ley said he was sur­prised at the emer­gence of a more-neg­a­tive tone from the agency’s pre­sen­ta­tion rel­a­tive to what was in­clud­ed with­in the FDA staff re­port post­ed two days pri­or, de­spite valid points made about the com­pa­ny’s risk mit­i­ga­tion plan.

Wil­ley wrote: “…the agency’s at­tempt to frame so­tagliflozin-me­di­at­ed DKA risk rel­a­tive to post-mar­ket­ing DKA events as­so­ci­at­ed with off-la­bel SGLT2i uti­liza­tion was in­her­ent­ly flawed. We’re not triv­i­al­iz­ing the risk here…How­ev­er, we do be­lieve the as­sump­tion of risk – par­tic­u­lar­ly for a drug which has sur­passed the re­quired ef­fi­ca­cy thresh­old in a dis­ease which has been ab­sent of in­no­va­tion since the ad­vent of in­sulin it­self – should be an in­di­vid­u­al­ized de­ci­sion made be­tween pa­tient/physi­cian…this same sto­ry has al­ready played out in the world of in­sulin pumps – where­by tran­si­tion­ing a type I di­a­betes pa­tient from in­jectable to pump-de­liv­ered in­sulin sig­nif­i­cant­ly in­creased DKA rates. Yet with suf­fi­cient pa­tient aware­ness/ed­u­ca­tion, these rates be­came man­age­able over time.”

Most an­a­lysts trimmed their ex­pec­ta­tions of the drug’s ap­proval for type I di­a­bet­ics.

Wil­ley said his mod­el still as­sumed a com­mer­cial launch in the US and EU in 2019, ac­knowl­edg­ing that the tim­ing was un­clear giv­en the re­sult of FDA pan­el meet­ing. He cut his 2021 US sales es­ti­mate to $245 mil­lion from $385 mil­lion. “If ap­proved, we still be­lieve this could prove to be a >$750M prod­uct in both the U.S. and EU with <12% mar­ket share amongst a grow­ing num­ber of type I di­a­bet­ic adults,” he not­ed.

Oth­er an­a­lysts were some­what more pes­simistic. Need­ham’s Alan Carr said he now be­lieves an FDA ap­proval in type I di­a­betes is pos­si­ble, but not prob­a­ble, and that he had elim­i­nat­ed the rev­enue stream from his mod­el. Cowen an­a­lysts, mean­while, were ready to throw in the tow­el, say­ing they now ex­pect an FDA re­jec­tion in March.

Lex­i­con’s shares $LXRX tum­bled about 25%, while Sanofi’s stock $SNY slipped about 1% in ear­ly trad­ing on Fri­day.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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Roche HQ in Basel, Switzerland. (Image credit: Kyle LaHucik/Endpoints News)

As com­peti­tors near FDA goal­post, Roche spells out its re­peat Alzheimer's set­back

Before Roche can turn all eyes on a new version of its more-than-once-failed Alzheimer’s drug gantenerumab, the Big Pharma had to flesh out data on the November topline failure at an annual conference buzzier than in years past thanks to hotly watched rivals in the field: Eisai and Biogen’s lecanemab, and Eli Lilly’s donanemab.

There was less than a 10% difference between Roche’s drug and placebo at slowing cognitive decline across two Phase III trials, which combined enrolled nearly 2,000 Alzheimer’s patients. In its presentation at the conference Wednesday, Roche said it saw less sweeping away of toxic proteins than it had anticipated. For years, researchers and investors have put their resources behind the idea that more amyloid removal would equate to reduced cognitive decline.

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Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

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Lynn Baxter, Viiv Healthcare's head of North America

Vi­iV dri­ves new cor­po­rate coali­tion in­clud­ing Uber, Tin­der and Wal­mart, aimed at end­ing HIV

ViiV Healthcare is pulling together an eclectic coalition of consumer businesses in a new White House-endorsed effort to end HIV by the end of the decade.

The new US Business Action to End HIV includes pharma and health companies — Gilead Sciences, CVS Health and Walgreens — but extends to a wide range of consumer companies that includes Tinder, Uber and Walmart.

ViiV is the catalyst for the group, plunking down more than half a million dollars in seed money and taking on ringmaster duties for launch today on World AIDS Day, but co-creator Health Action Alliance will organize joint activities going forward. ViiV and the alliance want and expect more companies to not only join the effort, but also pitch in funding.

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Matt Gline, Roivant Sciences CEO (Photo by John Sciulli/Getty Images for GLG)

Pfiz­er and Roivant team up again for an­oth­er 'Van­t', set­ting up an­ti-in­flam­ma­to­ry show­down with Prometheus

Pfizer and Roivant are teaming up to launch a new ‘Vant’ aimed at bringing a mid-stage anti-inflammatory drug to market, the pair announced Thursday.

There’s no name for the startup yet, nor are there any employees. Thus far, the new company and Roivant can be considered “one and the same,” Roivant CEO Matt Gline tells Endpoints News. But Pfizer is so enthusiastic about the target that it elected to keep 25% of equity in the drug rather than take upfront cash from Roivant, Gline said.

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SQZ Biotech slash­es head­count by 60% as founder/CEO hits ex­it — while Syn­log­ic lays off 25%

It’s a tough time for early-stage companies developing highly promising, but largely unproven, new technologies.

Just ask SQZ Biotechnologies and Synlogic. The former is bidding farewell to its founder and CEO and slashing the headcount by 60% as it pivots from its original cell therapy platform to a next-gen approach; the latter — a synthetic biology play founded by MIT’s Jim Collins and Tim Lu — is similarly “optimizing” the company to focus on lead programs. The resulting realignment means 25% of the staffers will be laid off.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

Twit­ter dis­ar­ray con­tin­ues as phar­ma ad­ver­tis­ers ex­tend paus­es and look around for op­tions, but keep tweet­ing

Pharma advertisers on Twitter are done — at least for now. Ad spending among the previous top spenders flattened even further last week, according to the latest data from ad tracker Pathmatics, amid ongoing turmoil after billionaire boss Elon Musk’s takeover now one month ago.

Among 18 top advertisers tracked for Endpoints News, only two are spending: GSK and Bayer. GSK spending for the full week through Sunday was minimal at just under $1,900. Meanwhile, German drugmaker Bayer remains the industry outlier upping its spending to $499,000 last week from $480,000 the previous week. Bayer’s spending also marks a big increase from a month ago and before the Musk takeover, when it spent $16,000 per week.

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