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.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.