Eli Lil­ly fi­nal­ly pub­lished its dis­as­trous EX­PE­DI­TION3 da­ta, a cost­ly les­son in re­think­ing Alzheimer's

Eli Lil­ly $LLY had hoped that EX­PE­DI­TION3 would prove to the world that amy­loid be­ta was the cause of Alzheimer’s and that solanezum­ab could bend the curve of cog­ni­tive de­cline back to pa­tients’ fa­vor — or at least for pa­tients with an ear­ly-stage, mild form of the dis­ease.

In­stead, the land­mark fail­ure — ac­knowl­edged well over a year ago — is rais­ing fresh ques­tions about whether in­ves­ti­ga­tors have been aim­ing at the wrong tar­get for more than a decade of flops and dis­as­trous fail­ures.

It took awhile, but Lil­ly fi­nal­ly laid out the last big round of EX­PE­DI­TION da­ta in the New Eng­land Jour­nal of Med­i­cine. And while solanezum­ab may have helped slow the mem­o­ry-wast­ing ail­ment, the im­pact was far too slight to make an im­por­tant dif­fer­ence for pa­tients.

Com­par­ing 1,057 pa­tients on drug com­pared to 1,072 on place­bo, the re­search team found a mod­est trend in its fa­vor:

The mean change from base­line in the ADAS-cog14 score was 6.65 in the solanezum­ab group of pa­tients with mild form of the dis­ease and 7.44 in the place­bo group, with no sig­nif­i­cant be­tween-group dif­fer­ence at week 80 (dif­fer­ence, −0.80; 95% con­fi­dence in­ter­val, −1.73 to 0.14; P=0.10)….The change from base­line in the MMSE score was −3.17 in the solanezum­ab group and −3.66 in the place­bo group.

John Lech­leit­er

And that’s where Lil­ly’s and for­mer CEO John Lech­leit­er’s dreams of cash­ing in a gold­en tick­et on a $10 bil­lion drug were fi­nal­ly ham­mered in­to scrap — though there is still work un­der­way to see if the drug can work to pre­vent the dis­ease from oc­cur­ring in the first place.

Lil­ly spent a for­tune on its three big tri­als of solanezum­ab, prod­ded on by not­ed Alzheimer’s re­searcher Paul Aisen. Every big fail­ure, though, in­spired a new hunt for da­ta that would back up a new the­o­ry of how it could work. And each fresh at­tempt went down to de­feat.

Now some in the field are start­ing to ask if the Alzheimer’s re­search com­mu­ni­ty should re­think the amy­loid the­o­ry, look­ing for new ev­i­dence on the con­flu­ence of events that cause the dis­ease.

In an ac­com­pa­ny­ing ed­i­to­r­i­al Paul Mur­phy from the Uni­ver­si­ty of Ken­tucky, Lex­ing­ton, wrote: “We may very well be near­ing the end of the amy­loid hy­poth­e­sis rope, at which point one or two more fail­ures will cause us to loosen our grip and let go.”

That would have ma­jor im­pli­ca­tions for Bio­gen and oth­ers, though, who are still bound and de­ter­mined to find the gold­en tick­et for them­selves. But that is look­ing more elu­sive than ever. In the mean­time, there’s a big dri­ve on to divvy up pa­tients in­to small­er, ge­net­i­cal­ly de­fined buck­ets in search of new drugs that could work. And there’s no sign that EX­PE­DI­TION3 or any oth­er set­back has de­flect­ed that sin­gu­lar­ly de­ter­mined set of in­ves­ti­ga­tors.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

David Berry (Flagship)

Flag­ship's next big tech­no­log­i­cal bet? The cloud

Earlier this month, Flagship announced their big bet on the software half the industry is talking about, launching the AI and machine learning startup. Now, they and a couple other investors are gambling $100 million on a software that much of the public generally thinks of as a cool, IT afterthought: cloud computing.

The idea, says founder and Flagship partner David Berry, is one of scale: The sheer magnitude of biological data that you can store on cloud technology is unprecedented. And that size, when leveraged properly, can allow you to ask questions and form insights that are similarly unprecedented.

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Covid-19 roundup: J&J be­gins piv­otal Phase III tri­al for vac­cine; Con­tro­ver­sial hu­man chal­lenge tri­als to be­gin in Lon­don — re­port

Johnson & Johnson announced it’s beginning a pivotal Phase III trial for its Covid-19 candidate, JNJ-78436735 — the first single-dose vaccine in this stage.

The Phase III trial, dubbed ENSEMBLE, will enroll 60,000 patients worldwide, making it the largest Phase III study of a Covid-19 vaccine to date. J&J said the candidate achieved positive interim results in a Phase I/IIa study, which will be published “imminently.” There’s a possibility that the first batches will be ready for potential emergency use in early 2021, according to the company.

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Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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