Tau­Rx takes a slice of pos­i­tive da­ta and claims suc­cess af­ter a failed PhI­II Alzheimer’s study

Tau­Rx raised more than $225 mil­lion from some un­con­ven­tion­al fi­nanc­ing sources to back their big pair of Phase III stud­ies for a new drug to treat Alzheimer’s. And they trav­eled to the Alzheimer’s As­so­ci­a­tion’s con­fer­ence in Toron­to to ac­knowl­edge that the first study failed on both end­points.

But that’s not stop­ping the com­pa­ny from claim­ing a suc­cess.

Tau­Rx CEO Claude Wis­chik says that in­ves­ti­ga­tors tracked a pos­i­tive re­sponse in a sub­group of pa­tients tak­ing the tau in­hibitor LMTX as a monother­a­py. And while he con­cedes he has no firm idea why that group ben­e­fit­ed when most pa­tients tak­ing a com­bi­na­tion of the drug with stan­dard of care showed ab­solute­ly iden­ti­cal re­spons­es to the con­trol arm, Tau­Rx switched the end­points on their sec­ond Phase III study — just ahead of the da­ta lock — to the rel­a­tive­ly small num­ber of pa­tients on monother­a­py. And he says they came up with a pos­i­tive read­out that could pave the way to an ap­proval.

The tri­al re­sults, claims Wis­chik, are un­prece­dent­ed in demon­strat­ing an im­prove­ment on cog­ni­tion and func­tion for Alzheimer’s pa­tients.

“We have hit the pri­ma­ry end­points,” the CEO tells me. “Whether that will con­sti­tute ad­e­quate ev­i­dence for prod­uct ap­proval, we can’t say.”

In the first failed Phase III, Wis­chik says about 15% of the pa­tients in the study were on monother­a­py. In the sec­ond, it was 20% of the pa­tients. And while Wis­chik con­cedes that he’s bas­ing his claim on an analy­sis of a sub­group of pa­tients in both Phase II­Is, he goes on to re­ject the no­tion that it’s a sub­group analy­sis. Af­ter mov­ing the goal posts in the sec­ond study, he’s de­clar­ing a touch­down on the pri­ma­ry end­points for the new­ly switched fo­cus group of pa­tients.

Un­like sev­er­al of the most ad­vanced drugs in the clin­ic for Alzheimer’s fo­cused on amy­loid be­ta, Wis­chik has been an out­spo­ken sup­port­er of the tau the­o­ry, point­ing to a tox­ic clus­ter found in the brains of many pa­tients with the mem­o­ry eras­ing dis­ease. But his tau in­hibitor LMTX, in com­bi­na­tion with stan­dard ther­a­pies, failed to sep­a­rate out from the rate of de­cline in cog­ni­tion and func­tion tracked in the con­trol arm.

The da­ta backed up the com­pa­ny’s con­tention that tau is a “very promis­ing drug de­vel­op­ment path­way,” Wis­chik not­ed. But he al­so goes on to say that he doesn’t un­der­stand why the monother­a­py would work while the com­bo didn’t.

“It’s a weak­ness,” says Wis­chik, but not nec­es­sar­i­ly a fa­tal one.

If that con­fu­sion is shared by reg­u­la­tors, though, it could well scut­tle LMTX’s chances of any near-term ap­proval.

In case af­ter case, where a Phase III has end­ed in fail­ure on the pri­ma­ry end­points, the de­vel­op­er has had to go back to the draw­ing board and ei­ther de­sign a new pro­gram with back to back stud­ies, or throw in the tow­el.

In Eli Lil­ly’s case, that meant tak­ing years and hun­dreds of mil­lions of dol­lars to tack­le the amy­loid be­ta drug solanezum­ab again. Lil­ly al­so moved the goal posts, though, drop­ping func­tion as a pri­ma­ry end­point even though reg­u­la­tors are still in­sist­ing on see­ing clear ev­i­dence of ef­fi­ca­cy on cog­ni­tion and func­tion. Oth­ers, like Glax­o­SmithK­line, have walked away af­ter a fail­ure. In GSK’s case, their drug was picked up for $5 mil­lion by Ax­o­vant, which de­signed a new Phase III tri­al for a clear­ly de­fined sub­group. Alzheon is tak­ing much the same strat­e­gy.

“They can’t get it ap­proved with this,” says one de­vel­op­er ac­tive­ly en­gaged in the field.

In ad­di­tion to be­ing equal­ly puz­zled about the hy­poth­e­sis of why the drug would work in this one sub­group and not the rest, the de­vel­op­er not­ed that reg­u­la­tors would still in­sist on a new Phase III pro­gram be­fore al­low­ing any drug to be mar­ket­ed to a mass group of des­per­ate pa­tients.

The gold stan­dard in drug de­vel­op­ment re­mains a ran­dom­ized, con­trolled prospec­tive Phase III tri­al, and reg­u­la­tors are un­like­ly to start com­pro­mis­ing on that point now.

Based in Sin­ga­pore with re­search fa­cil­i­ties in Scot­land, Tau­Rx was al­ways the odd duck among the flock of com­pa­nies tack­ling Alzheimer’s. Un­con­ven­tion­al fi­nanc­ing from the Malaysian casi­no and re­sort op­er­a­tor Genting Group un­der­scored part of the unique pic­ture, and al­so rais­es ques­tions of how the com­pa­ny could go about fund­ing a new pair of Phase III stud­ies with 800 to 900 pa­tients, which could eas­i­ly cost an­oth­er $200 mil­lion.

Tau­Rx has raised ex­pec­ta­tions of a pos­si­ble IPO at some point, as com­pa­ny of­fi­cials say that the ab­sence of any drug that blunts Alzheimer’s could cre­ate an in­stant mar­ket worth $10 bil­lion a year for a pi­o­neer like it­self. But there have been plen­ty of oth­ers who tried the same thing, on­ly to be beat back in a decade of R&D ef­forts that have met with uni­ver­sal de­feat in the clin­ic over the past decade.

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.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 81,800+ biopharma pros reading Endpoints daily — and it's free.

Ab­b­Vie wins an ap­proval in uter­ine fi­broid-as­so­ci­at­ed heavy bleed­ing. Are ri­vals My­ovant and Ob­sE­va far be­hind?

Women expel on average about 2 to 3 tablespoons of blood during their time of the month. But with uterine fibroids, heavy bleeding is typical — a third of a cup or more. Drugmakers have been working on oral therapies to try and stem the flow, and as expected, AbbVie and their partners at Neurocrine Biosciences are the first to make it across the finish line.

Known chemically as elagolix, the drug is already approved as a treatment for endometriosis under the brand name Orilissa. It targets the GnRH receptor to decrease the production of estrogen and progesterone.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 81,800+ biopharma pros reading Endpoints daily — and it's free.

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.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 81,800+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 81,800+ biopharma pros reading Endpoints daily — and it's free.

Roger Perlmutter, Merck R&D chief (YouTube)

UP­DAT­ED: Backed by BAR­DA, Mer­ck jumps in­to Covid-19: buy­ing out a vac­cine, part­ner­ing on an­oth­er and adding an­tivi­ral to the mix

Merck execs are making a triple play in a sudden leap into the R&D campaign against Covid-19. And they have more BARDA cash backing them up on the move.

Tuesday morning the pharma giant simultaneously announced plans to buy an Austrian biotech that has been working on a preclinical vaccine candidate, added a collaboration on another vaccine with the nonprofit IAVI and inked a deal with Ridgeback Biotherapeutics on an early-stage antiviral.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 81,800+ biopharma pros reading Endpoints daily — and it's free.

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.