Sci­en­tists toss an­oth­er Alzheimer’s pro­gram in­to the scrap heap as PhII fails

While a le­gion of sci­en­tists have been em­ployed in failed at­tempts to clear away the tox­ic tan­gles of pro­teins of­ten found in the brains of Alzheimer’s pa­tients, an­oth­er set have con­tin­ued to plug away at the var­i­ous chem­i­cals that play a role in or­ches­trat­ing the brain’s com­plex cel­lu­lar com­mu­ni­ca­tions sys­tem.

But that’s proved just as frus­trat­ing.

Jan Poth

To­day, Boehringer In­gel­heim threw in the tow­el on an Alzheimer’s pro­gram for a drug called BI 409306, an­oth­er ef­fort to see if they could do a bet­ter job in mod­u­lat­ing glu­ta­mate, one of those neu­ro­trans­mit­ters that can run amuck in de­men­tia.

The drug works by block­ing a pro­tein called PDE 9A which they be­lieved would en­hance cell sig­nal­ing in the glu­ta­mater­gic com­mand cen­ter in the brain. Re­searchers re­cruit­ed 457 pa­tients for two stud­ies, but like every­thing else that’s been put to a de­fin­i­tive test in the past 15 years, it failed to beat a place­bo in im­prov­ing cog­ni­tion.

It’s a log­i­cal field to ex­plore. Na­men­da was ap­proved by the FDA 15 years ago af­ter it was brought in from Eu­rope, where it had been used for years. That’s a glu­ta­mater­gic drug, fo­cus­ing on the NM­DA re­cep­tor — a big play­er in de­pres­sion. The drug tem­porar­i­ly mod­u­lates cog­ni­tive symp­toms of a dis­ease that grad­u­al­ly wipes out mem­o­ries.

Boehringer hasn’t giv­en up on the drug. It has plans to test it in schiz­o­phre­nia. And there’s a GlyT1 in­hibitor — an­oth­er glu­ta­mate drug called BI 425809 — which is be­ing test­ed in Alzheimer’s and oth­er CNS dis­eases.

The fail­ure rate for Alzheimer’s drug has been run­ning par­tic­u­lar­ly hot of late. We re­cent­ly got a close look at just how bad­ly Eli Lil­ly’s solanezum­ab failed to al­ter the course of the dis­ease by fo­cus­ing on amy­loid be­ta. Ax­o­vant cratered af­ter back-to-back fail­ures on a 5HT6 drug, an­oth­er symp­to­matic ef­fort fo­cused on a key neu­ro­trans­mit­ter. And Pfiz­er capped off the string of set­backs by call­ing it quits in the field, wip­ing out a pipeline of drugs and lay­ing off 300 peo­ple work­ing in the area.

Big play­ers like Bio­gen, though, con­tin­ue to in­vest heav­i­ly, con­vinced that they can suc­ceed where all oth­ers failed. And an up­start like De­nali can pull off a record-set­ting IPO by promis­ing to pur­sue new strate­gies.

But the odds in this field are par­tic­u­lar­ly tough, in an in­dus­try where fail­ure is a dai­ly re­al­i­ty.

“We recog­nise the im­mense an­tic­i­pa­tion around any progress in brain re­search that brings us clos­er to find­ing so­lu­tions for the many mil­lions of peo­ple liv­ing with de­men­tia. How­ev­er, this is what re­search is about: dis­ap­point­ments are a dai­ly ex­pe­ri­ence in sci­ence, but even these clin­i­cal tri­al re­sults will add to the un­der­stand­ing of brain func­tion and con­tribute to fu­ture progress in this area.” said Jan Poth, ther­a­peu­tic area head of CNS and im­munol­o­gy at Boehringer In­gel­heim.

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

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

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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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.

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 biotech.

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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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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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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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