Martin Tolar, Alzheon CEO

'Very over sol­d': Biotech brags about PhII Alzheimer's da­ta, but ex­perts are un­der­whelmed

In a field now de­fined by Bio­gen’s Aduhelm — and the storm of con­tro­ver­sy around it — what con­sti­tutes “in­dus­try-lead­ing” da­ta for an Alzheimer’s drug?

Alzheon, a lit­tle biotech de­vel­op­ing an oral amy­loid-clear­ing tablet, is tak­ing a stab at it.

Re­port­ing six-month da­ta from a Phase II bio­mark­er tri­al in­volv­ing 84 pa­tients, Alzheon an­nounced that ALZ-801, or valil­tramiprosate, spurred a 29% re­duc­tion in a bio­mark­er called plas­ma p-tau181 — which it said is sev­en-fold greater than that trig­gered by oth­er an­ti-amy­loid an­ti­bod­ies. Paired with “sig­nif­i­cant im­prove­ment” in a mem­o­ry test while not spec­i­fy­ing how much, the num­bers val­i­date its ap­proach and of­fer “a clear path for­ward with our mol­e­cules,” ac­cord­ing to CEO Mar­tin To­lar.

But a few ex­perts who re­viewed the press re­lease at End­points News’ re­quest dis­miss the re­sults as un­der­whelm­ing and weak.

“Very over sold,” George Per­ry, the neu­ro­bi­ol­o­gy chair at the Uni­ver­si­ty of Texas at San An­to­nio, wrote in an email.

The pri­ma­ry is­sue, he not­ed, is the lack of place­bo con­trols in the study. Fur­ther­more, Per­ry, a long­time skep­tic of the amy­loid hy­poth­e­sis in Alzheimer’s, ob­served that Alzheon has con­struct­ed its ar­gu­ment us­ing cor­re­la­tions that sim­ply haven’t been proven.

Al­though com­pa­nies have long tried to treat Alzheimer’s by get­ting rid of the amy­loid plaques and tau pro­tein tan­gles that build up in pa­tients’ brains, most of those ef­forts have un­suc­cess­ful. In no­table ex­am­ples — such as Bio­gen’s con­tro­ver­sial drug Aduhelm — com­pa­nies have dra­mat­i­cal­ly re­duced pa­tients’ amy­loid lev­els, while show­ing in­con­sis­tent or neg­li­gi­ble ef­fects on cog­ni­tion.

“There are NO stud­ies that show re­duc­tion of any form of amy­loid has cog­ni­tive ben­e­fit,” Per­ry said.

To­lar’s case is based on the premise that phos­pho­ry­lat­ed tau is pro­duced in re­ac­tion to sol­u­ble amy­loid oligomers, which are dis­tinct from in­sol­u­ble amy­loid plaques. Thus, “the amount of dam­age of the brain that trans­lates in­to clin­i­cal per­for­mance is ac­tu­al­ly linked to the lev­els of the p-tau. And al­so it dy­nam­i­cal­ly cor­re­lates with the ef­fec­tive treat­ment.”

As a sec­ondary out­come, Alzheon al­so mea­sured pa­tients’ per­for­mance on a learn­ing and mem­o­ry test called the Au­di­to­ry Ver­bal Learn­ing Test (RAVLT). With­out dis­clos­ing the nu­mer­i­cal im­prove­ment, the com­pa­ny said there is an im­prove­ment from base­line at week 26, with a p-val­ue of 0.002.

When pressed, he de­clined to elab­o­rate on the mag­ni­tude of ben­e­fit, choos­ing in­stead to talk about the bur­den Alzheimer’s pa­tients face and the mean­ing of im­prove­ment.

“ADL is still the coin of the realm,” wrote Sam Gandy, the Mount Sinai pro­fes­sor of Alzheimer’s Dis­ease Re­search, re­fer­ring to a stan­dard met­ric for ac­tiv­i­ties of dai­ly liv­ing. “If there is no mean­ing­ful func­tion­al ben­e­fit, I would be un­der­whelmed.”

Still, Alzheon does have its sup­port­ers. Howard Fil­lit, co-founder and chief sci­ence of­fi­cer at the Alzheimer’s Drug Dis­cov­ery Foun­da­tion, called the re­sults “im­pres­sive” and the tri­al “well de­signed, with a fo­cus on pa­tients with APOE4 — i.e., those at the high­est risk.”

“I al­so want to note the mech­a­nism of ac­tion is plau­si­ble and based on ex­ten­sive sci­ence,” Fil­lit wrote in an email. “This ap­proach has been in de­vel­op­ment for over 30 years, and was first test­ed by a biotech com­pa­ny based in Cana­da named Neu­rochem, which con­duct­ed a large Phase III tri­al of a re­lat­ed drug pri­or to the era of ‘mod­ern’ bio­mark­ers and clin­i­cal tri­al de­sign.”

The NIH gave Alzheon a $47 mil­lion grant to run a Phase III tri­al, for which it’s en­rolling pa­tients. To­lar hopes the study, which will re­cruit around 1,000 pa­tients and em­ploy the gold-stan­dard pri­ma­ry end­point of ADAS-Cog 13, could serve as the ba­sis for ap­proval.

Re­flect­ing on the con­tro­ver­sy around Bio­gen’s Aduhelm, To­lar ac­knowl­edged the de­bate around the drug’s ef­fec­tive­ness and ques­tioned the use of amy­loid plaque re­moval as a sur­ro­gate end­point.

“Yes, it’s been chal­leng­ing, you know, be­cause it’s been on the front page, and all over the me­dia, these is­sues around Bio­gen and Aduhelm,” he said. “But, you know, again, I mean, I think we need to go and treat pa­tients, you know, and have a very com­pelling ev­i­dence for ef­fi­ca­cy.”

Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls

Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Matt Gline, Roivant Sciences CEO (Photo by John Sciulli/Getty Images for GLG)

Pfiz­er and Roivant team up again for an­oth­er 'Van­t', set­ting up an­ti-in­flam­ma­to­ry show­down with Prometheus

Pfizer and Roivant are teaming up to launch a new ‘Vant’ aimed at bringing a mid-stage anti-inflammatory drug to market, the pair announced Thursday.

There’s no name for the startup yet, nor are there any employees. Thus far, the new company and Roivant can be considered “one and the same,” Roivant CEO Matt Gline tells Endpoints News. But Pfizer is so enthusiastic about the target that it elected to keep 25% of equity in the drug rather than take upfront cash from Roivant, Gline said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

Roche HQ in Basel, Switzerland. (Image credit: Kyle LaHucik/Endpoints News)

As com­peti­tors near FDA goal­post, Roche spells out its re­peat Alzheimer's set­back

Before Roche can turn all eyes on a new version of its more-than-once-failed Alzheimer’s drug gantenerumab, the Big Pharma had to flesh out data on the November topline failure at an annual conference buzzier than in years past thanks to hotly watched rivals in the field: Eisai and Biogen’s lecanemab, and Eli Lilly’s donanemab.

There was less than a 10% difference between Roche’s drug and placebo at slowing cognitive decline across two Phase III trials, which combined enrolled nearly 2,000 Alzheimer’s patients. In its presentation at the conference Wednesday, Roche said it saw less sweeping away of toxic proteins than it had anticipated. For years, researchers and investors have put their resources behind the idea that more amyloid removal would equate to reduced cognitive decline.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

SQZ Biotech slash­es head­count by 60% as founder/CEO hits ex­it — while Syn­log­ic lays off 25%

It’s a tough time for early-stage companies developing highly promising, but largely unproven, new technologies.

Just ask SQZ Biotechnologies and Synlogic. The former is bidding farewell to its founder and CEO and slashing the headcount by 60% as it pivots from its original cell therapy platform to a next-gen approach; the latter — a synthetic biology play founded by MIT’s Jim Collins and Tim Lu — is similarly “optimizing” the company to focus on lead programs. The resulting realignment means 25% of the staffers will be laid off.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

Lynn Baxter, Viiv Healthcare's head of North America

Vi­iV dri­ves new cor­po­rate coali­tion in­clud­ing Uber, Tin­der and Wal­mart, aimed at end­ing HIV

ViiV Healthcare is pulling together an eclectic coalition of consumer businesses in a new White House-endorsed effort to end HIV by the end of the decade.

The new US Business Action to End HIV includes pharma and health companies — Gilead Sciences, CVS Health and Walgreens — but extends to a wide range of consumer companies that includes Tinder, Uber and Walmart.

ViiV is the catalyst for the group, plunking down more than half a million dollars in seed money and taking on ringmaster duties for launch today on World AIDS Day, but co-creator Health Action Alliance will organize joint activities going forward. ViiV and the alliance want and expect more companies to not only join the effort, but also pitch in funding.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

AbCellera founder and CEO Carl Hansen (L) and Rallybio CEO Martin Mackay

Rally­bio, Ab­Cellera form new part­ner­ship around an­ti­bod­ies for rare dis­ease

Two biotechs that have been working heavily on different stages of antibody candidate development over the past several years are looking to work together to find potential candidates for rare diseases.

Canadian-based AbCellera and Connecticut-based Rallybio have entered a strategic partnership to find, develop and commercialize antibodies primarily for rare diseases. The multi-year, multi-target deal will seek to combine AbCellera’s antibody “discovery engine” with Rallybio’s expertise in rare diseases. However, the dollar amount for the deal was not disclosed.