As­traZeneca wants a do-over on MYS­TIC com­bo da­ta. But a change­up in fo­cus won’t end the death watch on this pair­ing

As­traZeneca CEO Pas­cal So­ri­ot’s de­ci­sion to bet big on a check­point R&D strat­e­gy that re­lied heav­i­ly on its in-house com­bo of PD-L1 and CT­LA-4 is start­ing to look like a block­buster los­er. And this week’s push­back on a sub­set of the da­ta re­lat­ed to high tu­mor mu­ta­tion bur­den will like­ly do very lit­tle to change the odds here.

Bioreg­num Opin­ion Col­umn by John Car­roll

Re­searchers for the phar­ma gi­ant $AZN turned up at the Eu­ro­pean So­ci­ety for Med­ical On­col­o­gy Im­muno-On­col­o­gy 2018 Con­gress in Gene­va this week with more stun­ning­ly poor da­ta for the com­bi­na­tion of Imfinzi and treme­li­mum­ab, which was out­per­formed by Imfinzi alone — though the monother­a­py al­so failed to stand out in ad­vanced cas­es of non-small cell lung can­cer.

We al­ready knew that the haz­ard ra­tio for the com­bi­na­tion was a poor 0.85, but Imfinzi’s 24-month over­all sur­vival rate was 38.3% com­pared to an em­bar­rass­ing 35.4% for the PD-L1 plus CT­LA-4 ap­proach.

From As­traZeneca:

Among pa­tients re­ceiv­ing Imfinzi, 40.4% of pa­tients ex­pe­ri­enced a grade 3 or 4 ad­verse event (AE) vs. 47.7% with the Imfinzi plus treme­li­mum­ab com­bi­na­tion and 46.0% with chemother­a­py. 5.4% of pa­tients dis­con­tin­ued Imfinzi due to treat­ment-re­lat­ed AEs vs. 13.2% with the com­bi­na­tion and 9.4% on chemother­a­py.

Chloé Thé­paut

The com­pa­ny’s re­search team, though, was hop­ing to pull a vic­to­ry out of the mouth of de­feat by point­ing to a much bet­ter per­for­mance among pa­tients iden­ti­fied with a high tu­mor mu­ta­tion bur­den — putting them on the ex­act same path that Bris­tol-My­ers Squibb has tried to em­ploy with Op­di­vo plus Yer­voy. In that group there was a 36% drop in risk of death, with a haz­ard ra­tion of 0.64.

That would have to be con­firmed in a new study, though, be­fore reg­u­la­tors would con­sid­er it for ap­proval — which may in turn spur an­oth­er fol­low-up to Bris­tol-My­ers with a change­up in an on­go­ing tri­al to bring that clos­er to re­al­i­ty.

Bris­tol-My­ers’ own ap­proach to carv­ing out mar­ket share among TMB pa­tients, though, has failed to im­press an­a­lysts as more da­ta came out. Cred­it Su­isse in par­tic­u­lar not­ed a sim­i­lar­i­ty in sur­vival ben­e­fit for the low and high TMB groups in Bris­tol-My­ers’ da­ta set, which bodes ill for their mar­ket prospects.

And all of this is play­ing out as Mer­ck con­tin­ues to rack up big gains us­ing a com­bi­na­tion of Keytru­da and chemo in lung can­cer, which in­creas­ing­ly gains strength as the right com­bo to turn to ini­tial­ly to im­prove per­for­mance.

CT­LA-4 al­ready has a bad rep­u­ta­tion for tox­i­c­i­ty and mar­gin­al OS im­prove­ments that’s made it a tar­get for oth­ers look­ing to do bet­ter. Even­tu­al­ly, Yer­voy is like­ly to go down in his­to­ry as the check­point that re­vealed where these ther­a­pies could go. It was a mas­sive­ly im­por­tant start­ing point in a sto­ry that has many chap­ters to come.

Mean­while, the tidal wave of check­points and com­bo tri­als is com­ing up on the hori­zon, with plen­ty of op­por­tu­ni­ties for some­one else to make their mark as As­traZeneca con­tin­ues to fo­cus on MYS­TIC and treme­li­mum­ab.

But that game may al­ready be over, es­pe­cial­ly af­ter an­oth­er read­out for the As­traZeneca com­bo just days ago un­der­scored its fail­ure in head and neck can­cer.

Ear­li­er this week, Chloé Thé­paut, se­nior on­col­o­gy an­a­lyst for Glob­al­Da­ta, put it like this:

Un­less da­ta in fur­ther in­di­ca­tions, such as that ex­pect­ed from the KESTREL tri­al, can demon­strate su­pe­ri­or­i­ty of Imfinzi + treme­li­mum­ab over the stan­dard-of-care, or show im­pres­sive ef­fi­ca­cy or promis­ing safe­ty ver­sus com­pet­ing com­bi­na­tions, it is un­like­ly that As­traZeneca will have a dif­fer­en­ti­a­tion point suf­fi­cient for the com­bi­na­tion to be tak­en up on­to the mar­ket.

It may not be time yet to pre­pare the eu­lo­gy on this one, but it’s al­ready on death watch.

Im­age: Pas­cal So­ri­ot. GET­TY IM­AGES

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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Paul Hudson, Sanofi CEO (ROMUALD MEIGNEUX/Sipa via AP Images)

Sanofi and Am­gen are bring­ing cash to cov­er the ta­ble stakes for the Hori­zon M&A game

With the market cap on Horizon Therapeutics $HZNP pushed up to the $23 billion mark today, one of the Big Pharmas in the hunt for a major league buyout deal signaled it’s playing the M&A game with cash.

Paris-based Sanofi, where CEO Paul Hudson has been largely focused on some risky biotech acquisitions to win some respect for its future pipeline prospects, issued a statement early Friday — complying with rule 2.12 of the Irish takeover rules — making clear that while the certainty or size of an offer can’t be determined, any offer “will be solely in cash.” And Amgen CEO Robert Bradway came right in behind him, filing a statement on the London Stock Exchange overnight that any offer they may make will “likely” be in cash as well.

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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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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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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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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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Paul Hudson, Sanofi CEO (Romuald Meigneux/Sipa via AP Images)

Sanofi and DN­Di aim to elim­i­nate sleep­ing sick­ness in Africa with promis­ing Ph II/III re­sults for new drug

The Drugs for Neglected Diseases initiative (DNDi) and Sanofi today said that their potential sleeping sickness treatment saw success rates of up to 95% from a Phase II/III study investigating the safety and efficacy of single-dose acoziborole.

The potentially transformative treatment for sleeping sickness would mainly be targeted at African countries, according to data published today in The Lancet Infectious Diseases medical journal. The clinical trial was led by DNDi and its partners in the Democratic Republic of the Congo (DRC) and Guinea, with the authors noting: