Af­ter yet an­oth­er PhI­II Alzheimer's fail­ure, ex­perts try to map a path out of the wreck­ing field

Pushed by a 15-year record of clin­i­cal fail­ures and pulled by an FDA search­ing for a prac­ti­cal new path for­ward for Alzheimer’s drug re­search, a joint com­mit­tee or­ga­nized by the NIH’s Na­tion­al In­sti­tute of Ag­ing and the Alzheimer’s As­so­ci­a­tion is sug­gest­ing a bio­mark­er-based ap­proach to defin­ing the ill­ness that can guide new de­vel­op­ment ef­forts.

Eliez­er Masli­ah

In place of the old tox­ic pro­tein de­bate that once di­vid­ed the field in­to two camps for amy­loid be­ta and tau, the group be­lieves that the pres­ence of both should be a hall­mark of Alzheimer’s, along with phys­i­cal ev­i­dence of neu­rode­gen­er­a­tion or neu­ronal in­jury. By mix­ing and match­ing the bio­mark­ers, they want to be able to high­light the de­vel­op­ment of the dis­ease in­to a set of dis­tinct stages that can be used to test the ef­fec­tive­ness of new drugs and com­bi­na­tion ther­a­pies even be­fore symp­toms ap­pear.

So amy­loid be­ta by it­self would be ev­i­dence of dis­ease pathol­o­gy. Added to the pres­ence of tau you could di­ag­nose some­one as hav­ing Alzheimer’s. And signs of neu­rode­gen­er­a­tion could be used to high­light the ad­vance of the dis­ease. They’re al­so leav­ing the door open to oth­er bio­mark­ers for the dis­ease as re­search con­tin­ues and the field evolves.

By cen­ter­ing on bio­mark­ers that can be iden­ti­fied through brain imag­ing, along with a stan­dard ap­proach to defin­ing cog­ni­tion, they be­lieve they have a foun­da­tion to build a new wave of stud­ies that can find new drugs to help the mil­lions of peo­ple who un­know­ing­ly have the first tell­tale signs of a lethal dis­ease that wipes out a per­son’s mem­o­ries.

“We have to fo­cus on bi­o­log­i­cal or phys­i­cal tar­gets to ze­ro in on po­ten­tial treat­ments for Alzheimer’s,” ex­plained Eliez­er Masli­ah, di­rec­tor of the di­vi­sion of neu­ro­science at the NIA. “By shift­ing the dis­cus­sion to neu­ropatho­log­ic changes de­tect­ed in bio­mark­ers to de­fine Alzheimer’s, as we look at symp­toms and the range of in­flu­ences on de­vel­op­ment of Alzheimer’s, I think we have a bet­ter shot at find­ing ther­a­pies, and soon­er.”

Their pro­pos­al is crit­i­cal to a big R&D field that has been shak­en by a se­ries of ma­jor drug stud­ies that have gone far to prove that re­searchers don’t have a clear un­der­stand­ing of the bi­ol­o­gy of the dis­ease. 

Lon Schnei­der

“You can’t get around that peo­ple can have the pathol­o­gy of Alzheimer’s dis­ease and not have clin­i­cal symp­toms,” Lon Schnei­der, a re­searcher at USC’s Keck School of Med­i­cine, told me re­cent­ly as I ex­plored where the field was head­ed. “They can have a head full of amy­loid and be at risk of de­vel­op­ing de­men­tia,” but then nev­er ex­pe­ri­ence symp­toms of the dis­ease.

The news on Alzheimer’s R&D is all bad. Mer­ck’s re­cent de­ci­sive fail­ure on BACE, cut­ting off the sup­ply of amy­loid be­ta to the brains of pa­tients, has helped dis­prove a the­o­ry that has spurred bil­lions in fresh re­search spend­ing. Just yes­ter­day lit­tle vTv threw in the tow­el on an at­tempt to re­pur­pose a failed drug from Pfiz­er for the dis­ease, an­oth­er chron­ic los­er among var­i­ous de­vel­op­ment strate­gies. And Pfiz­er, af­ter spend­ing bil­lions of dol­lars on var­i­ous projects, opt­ed to sim­ply drop out, join­ing an in­dus­try re­treat that has al­ready claimed the li­on’s share of the work at As­traZeneca and Glax­o­SmithK­line. 

Richard Hodes

At the same time, the FDA has been en­cour­ag­ing the field to de­fine a stan­dard set or bio­mark­ers that could help de­fine a path for re­searchers to rea­son­ably de­fine the dis­ease and demon­strate progress in slow­ing it down, ahead of symp­toms de­fined by the gold stan­dard of Phase III pro­grams cen­tered on cog­ni­tion and func­tion. 

“In the con­text of con­tin­u­ing evo­lu­tion of Alzheimer’s re­search and tech­nolo­gies, the pro­posed re­search frame­work is a log­i­cal next step to help the sci­en­tif­ic com­mu­ni­ty ad­vance in the fight against Alzheimer’s,” said NIA Di­rec­tor Richard Hodes. “The more ac­cu­rate­ly we can char­ac­ter­ize the spe­cif­ic dis­ease process patho­log­i­cal­ly de­fined as Alzheimer’s dis­ease, the bet­ter our chances of in­ter­ven­ing at any point in this con­tin­u­um, from pre­vent­ing Alzheimer’s to de­lay­ing pro­gres­sion.”

Their work is in the April 10 is­sue of Alzheimer’s & De­men­tia: The Jour­nal of the Alzheimer’s As­so­ci­a­tion.

As­traZeneca trum­pets the 'mo­men­tous' da­ta they found for Tagris­so in an ad­ju­vant set­ting for NSCLC — but many of the ex­perts aren’t cheer­ing along

AstraZeneca is rolling out the big guns this evening to provide a salute to their ADAURA data on Tagrisso at ASCO.

Cancer R&D chief José Baselga calls the disease-free survival data for their drug in an adjuvant setting of early stage, epidermal growth factor receptor-mutated NSCLC patients following surgery “momentous.” Roy Herbst, the principal investigator out of Yale, calls it “transformative.”

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The Avance Clinical leadership team: CEO Yvonne Lungershausen, Sandrien Louwaars - Director Business Development Operations, Gabriel Kremmidiotis - Chief Scientific Officer, Ben Edwards - Chief Strategy Officer

How Aus­tralia De­liv­ers Rapid Start-up and 43.5% Re­bate for Ear­ly Phase On­col­o­gy Tri­als

About Avance Clinical

Avance Clinical is an Australian owned Contract Research Organisation that has been providing high-quality clinical research services to the local and international drug development industry for 20 years. They specialise in working with biotech companies to execute Phase 1 and Phase 2 clinical trials to deliver high-quality outcomes fit for global regulatory standards.

As oncology sponsors look internationally to speed-up trials after unprecedented COVID-19 suspensions and delays, Australia, which has led the world in minimizing the pandemic’s impact, stands out as an attractive destination for early phase trials. This in combination with the streamlined regulatory system and the financial benefits including a very favourable exchange rate and the R & D cash rebate makes Australia the perfect location for accelerating biotech clinical programs.

David Chang, Allogene CEO (Jeff Rumans)

Head­ed to PhII: Al­lo­gene CEO David Chang com­pletes a pos­i­tive ear­ly snap­shot of their off-the-shelf CAR-T pi­o­neer

Allogene CEO David Chang has completed the upbeat first portrait of the biotech’s off-the-shelf CAR-T contender ALLO-501 at virtual ASCO today, keeping all eyes on a drug that will now try to go on to replace the first-wave personalized pioneers he helped create.

The overall response rate outlined in Allogene’s abstract for treatment-resistant patients with non-Hodgkin lymphoma slipped a little from the leadup, but if you narrow the patient profile to treatment-naïve patients — removing the 3 who had previous CAR-T therapy who didn’t respond, leaving 16 — the ORR lands at 75% with a 44% complete response rate. And 9 of the 12 responders remained in response at the data cutoff, offering a glimpse on durability that still has a long way to go before it can be completely nailed down.

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Pablo Legorreta, founder and CEO of Royalty Pharma AG, speaks at the annual Milken Institute Global Conference in Beverly Hills, California (Patrick T. Fallon/Bloomberg via Getty Images)

Cap­i­tal­iz­ing Pablo: The world’s biggest drug roy­al­ty buy­er is go­ing pub­lic. And the low-key CEO di­vulges a few se­crets along the way

Pablo Legorreta is one of the most influential players in biopharma you likely never heard of.

Over the last 24 years, Legorreta’s Royalty Pharma group has become, by its own reckoning, the biggest buyer of drug royalties in the world. The CEO and founder has bought up a stake in a lengthy list of the world’s biggest drug franchises, spending $18 billion in the process — $2.2 billion last year alone. And he’s become one of the best-paid execs in the industry, reaping $28 million from the cash flow last year while reserving 20% of the cash flow, less expenses, for himself.

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Fabrice Chouraqui, Cellarity CEO-partner (LinkedIn)

Drug de­vel­op­er, Big Phar­ma com­mer­cial ex­ec, now an up­start biotech chief — Fab­rice Chouraqui is ready to try some­thing new as a ‘CEO-part­ner’ at Flag­ship

Fabrice Chouraqui’s career has taken some big twists along his life journey. He got his PharmD at Université Paris Descartes and jumped into the drug development game for a bit. Then he took a sharp turn and went back to school to get his MBA at Insead before returning to pharma on the commercial side.

Twenty years later, after steadily rising through the ranks and journeying the globe to nab a top job as president of US pharma for the Basel-based Novartis, Chouraqui exited in another career switch. And now he’s headed into a hybrid position as a CEO-partner at Flagship, where he’ll take a shot at leading Cellarity — one of the VC’s latest paradigm-changing companies of the groundbreaking model that aspires to deliver a new platform to the world of drug R&D.

Paul Hudson, Sanofi CEO (Getty Images)

Sanofi CEO Paul Hud­son has $23B burn­ing a hole in his pock­et. And here are some hints on how he plans to spend that

Sanofi has reaped $11.1 billion after selling off a big chunk of its Regeneron stock at $515 a share. And now everyone on the M&A side of the business is focused on how CEO Paul Hudson plans to spend it.

After getting stung in France for some awkward politicking — suggesting the US was in the front of the line for Sanofi’s vaccines given American financial support for their work, versus little help from European powers — Hudson now has the much more popular task of managing a major cash cache to pull off something in the order of a big bolt-on. Or two.

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As­traZeneca’s $7B ADC suc­ceeds where Roche failed, im­prov­ing sur­vival in gas­tric can­cer

Another day, another win for Enhertu.

The antibody-drug conjugate AstraZeneca promised up-to $7 billion to partner on has had a quite a few months, beginning with splashy results in a Phase II breast cancer trial, a rapid approval and, earlier this month, breakthrough designations in both non-small cell lung cancer and gastric cancer.

Now, at ASCO, the British pharma and their Japanese partner, Daiichi Sankyo, have shown off the data that led to the gastric cancer designation, which they’ll take back to the FDA. In a pivotal, 187-person Phase II trial, Enhertu shrunk tumors in 42.9% of third-line patients with HER2-positive stomach cancer, compared with 12.5% in a control arm where doctors prescribed their choice of therapy. Progression-free survival was 5.4 months for Enhertu compared to 3.5 months for the control.

Once a gem, now just a rock, Take­da punts PhI­II IBD drug as ri­vals mus­cle ahead

Back in 2016, when then-Shire CEO Flemming Ørnskov picked up a promising clinical-stage IBD drug from Pfizer, the Boston-based biotech dubbed it SHP647 and moved it into the gem section of the pipeline, with rosy expectations of registration-worthy Phase III data ahead.

This was a drug that the EC wanted Takeda to commit to selling off before it gave their blessing to its acquisition of Shire, to settle some deep-seated concerns revolving around the potential market overlap with their blockbuster rival Entyvio. And Takeda, which took on a heavy debt load to buy Shire, clearly wanted the cash to pay down debt.

Ear­ly sur­vival da­ta boost Zio­phar­m's 'con­trolled IL-12' im­munother­a­py for glioblas­toma

An unconventional pairing of a gene therapy and an oral drug that promises to attack recurrent or progressive glioblastoma with controlled release of IL-12 has turned up more promising — if early — overall survival data. On top of boosting its case as a monotherapy, the data can also bode well for a combination with Regeneron’s PD-1 inhibitor, Libtayo.

Both the treatment and its developer, Ziopharm Oncology, have come a long way. The stock price peaked in 2015 but cratered in 2016 following a patient death in a Phase I.