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.

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,300+ biopharma pros reading Endpoints daily — and it's free.

GSK's asth­ma bi­o­log­ic Nu­cala scores in rare blood dis­or­der study

GlaxoSmithKline’s asthma drug Nucala, which received a resounding FDA rejection for use in chronic obstructive pulmonary disease (COPD) last year, has shown promise in a rare blood disorder.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,300+ biopharma pros reading Endpoints daily — and it's free.

Mer­ck buys a fledg­ling neu­rode­gen­er­a­tive biotech spawned by an old GSK dis­cov­ery al­liance. What’s up with that?

Avalon Ventures chief Jay Lichter has a well-known yen for drug development programs picked up in academia. And what he found in Haoxing Xu’s lab at the University of Michigan pricked his interest enough to launch one of his umbrella biotechs in San Diego.
Xu’s work laid the foundation for Avalon to launch Calporta, which has been working on finding small molecule agonists of TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) for lysosomal storage disorders. And that pathway, they believe, points to new approaches on major market neurodegenerative diseases like Parkinson’s, ALS and Alzheimer’s.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,300+ biopharma pros reading Endpoints daily — and it's free.

FDA slaps a hold on an AML tri­al as Mark­er scraps a fail­ing ovar­i­an can­cer pro­gram, sink­ing shares

The FDA has placed a hold on a Phase II AML trial from the small immuno-oncology biotech Marker Therapeutics. Marker disclosed the issue two weeks after responding to FDA concerns, adding it to the Q3 release Tuesday. The company also announced it was scrapping a Phase II ovarian cancer program it determined was unlikely to succeed.

The agency’s concern centers around two reagents used in manufacturing for their trial for acute myeloid leukemia patients who have received a stem cell transplant. The reagents are from third parties and not present in the final product, Marker said.

Eli Lil­ly-backed biotech grabs $100M to dis­patch an­ti­body-oligonu­cleotide con­ju­gates af­ter mus­cu­lar dy­s­tro­phy

Hold up your hand. Make a fist. Now open it. And again.

If you can do it fully and with ease, then the proteins in your hand are likely working properly. If you can’t then they may not be. In people with myotonic muscular dystrophy, something more atomic is going on.

In those folks, the problem is RNA. Certain base pairs repeat far beyond normal, up to 11,000 superfluous letters in some cases. The extended strands form “clumps.” Proteins misform and can’t function properly. They often allow one movement but not the reverse, a condition called myotonia that gives the dystrophy its name.

As­traZeneca sets stage for mar­ket­ing ap­pli­ca­tion with promis­ing piv­otal lu­pus drug da­ta

After fumbling in its first late-stage lupus study, AstraZeneca disclosed that a second pivotal trial testing its experimental drug, anifrolumab, had met the main goal, in August. Earlier this week, the British drugmaker broke out the numbers from its successful study.

Last year, anifrolumab failed to meet the main goal of diminishing disease activity in the 460-patient TULIP I study, a 52-week trial that tested two doses of the drug versus a placebo. But in the 373-patient TULIP II study, the higher dose (300 mg) was compared to patients given a placebo — patients in both arms were on baseline standard care.

FDA Vas­cepa re­view spot­lights new safe­ty sig­nals, pos­si­ble min­er­al oil spoil­er as Amarin hunts a block­buster ap­proval

An in-house FDA review of Amarin’s Vascepa raises a set of hurdles the biotech will have to clear if the biotech expects to get the long-awaited FDA approval that could set it on a path to superstar status. But it appears that Amarin has survived another potential setback without introducing a major new threat to its prospects.

The stakes don’t get much higher, with analysts saying a win this week for Amarin could lead to billions in new sales — provided the agency stamps it with an OK. And investors liked what they say in the FDA review this morning, bumping the stock $AMRN 17%.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,300+ biopharma pros reading Endpoints daily — and it's free.

FDA puts Sol­id Bio’s lead gene ther­a­py pro­gram on hold — again — af­ter an­oth­er pa­tient is hurt by SGT-001

Solid Biosciences continues to be plagued by safety issues.

Close to 18 months after the gene therapy biotech was able to quickly shed an FDA hold on their lead Duchenne muscular dystrophy program for SGT-001, regulators have stepped back in to force another halt after another patient was hit hard by a set of serious adverse events remarkably similar to the first set.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,300+ biopharma pros reading Endpoints daily — and it's free.