A year af­ter stun­ning Chi­na OK, Shang­hai Alzheimer's drug­mak­er set to en­roll first US pa­tient — and the stakes are huge

Just as ex­perts are set to de­bate whether Bio­gen’s ad­u­canum­ab should be­come the first Alzheimer’s drug to be ap­proved in the US in al­most two decades, a ther­a­py that seized a con­di­tion­al OK in Chi­na late last year — shock­ing sci­en­tists around the world — is fi­nal­ly mak­ing head­way in the clin­ic.

The US arm of Shang­hai Green Val­ley’s glob­al Phase III tri­al has iden­ti­fied its first pa­tient, Bloomberg re­port­ed, and dos­ing will be­gin in four weeks.

Even the ear­li­est da­ta like­ly won’t be­come avail­able un­til 2026, as Green Val­ley es­ti­mates pri­ma­ry com­ple­tion to be De­cem­ber 2025 on its clin­i­cal­tri­als.gov post­ing. But the re­sults will be high-stakes as an in­di­ca­tion of not just Chi­na’s drug R&D prowess but its reg­u­la­to­ry stan­dards. Did an ob­scure Chi­nese biotech tru­ly de­liv­er an ef­fec­tive treat­ment for a dis­ease that’s de­fied all West­ern so­lu­tions? Or did reg­u­la­tors, in­ten­tion­al­ly or un­in­ten­tion­al­ly, clear a use­less place­bo in ser­vice of boast­ing rights?

Clar­i­ty Clin­i­cal Re­search, an Alzheimer’s fo­cused group based out of New York state, is help­ing screen pa­tients for the study — which is de­signed to re­cruit 2046 par­tic­i­pants across the US, Chi­na and Eu­rope.

Green Val­ley is re­serv­ing $600 mil­lion for the Phase III tri­al, Bloomberg not­ed, as part of a $3 bil­lion in­vest­ment in­to elu­ci­dat­ing and prov­ing the un­der­ly­ing mech­a­nisms of GV-971.

Hav­ing launched the drug last De­cem­ber at $134.52 per box, in Ju­ly the com­pa­ny be­gan con­struc­tion on a $180 mil­lion new man­u­fac­tur­ing fa­cil­i­ty in Shang­hai ded­i­cat­ed to ex­ports and built-in ac­cor­dance with GMP re­quire­ments in Chi­na, the US and Eu­rope. It ex­pects the site to come on­line by the end of 2024.

The ini­ti­a­tion has been a long way com­ing. As soon as it scored con­di­tion­al ap­proval in Chi­na last year, the biotech had said it would launch a glob­al pro­gram in ear­ly 2020. But while the FDA green­light­ed the tri­al in April, amid the Covid-19 pan­dem­ic Green Val­ley was ap­par­ent­ly un­able to meet its stat­ed start date in Oc­to­ber.

Giv­en as oral cap­sules, the drug con­sists of oligo­man­nate, an oligosac­cha­ride de­rived from sea­weeds. While the re­searchers had ini­tial­ly thought it may work by al­ter­ing amy­loid be­ta — the dom­i­nant tar­get that crit­ics say should be dead by now — they ul­ti­mate­ly pro­posed that “GV-971 ther­a­peu­ti­cal­ly har­ness­es the ab­nor­mal pro­duc­tion of amino acids, in­fil­tra­tion of im­mune cells to the brain, and in turn neu­roin­flam­ma­tion via re­mod­el­ling the gut mi­cro­bio­ta.”

Based on its first Phase III, which re­cruit­ed pa­tients in Chi­na on­ly, Green Val­ley claimed that it im­proved cog­ni­tive func­tions in pa­tients with mild-to-mod­er­ate Alzheimer’s.

It had some promi­nent al­lies in its cor­ner. Er­ic Reiman, ex­ec­u­tive di­rec­tor of Ban­ner Alzheimer’s In­sti­tute, is a sci­en­tif­ic ad­vis­er along­side renowned re­searchers Jef­frey Cum­mings and Philip Schel­tens, ap­plaud­ing the safe­ty pro­file of the drug and how it di­ver­si­fies the port­fo­lio. IQVIA and Sig­nant Health lend­ed some se­ri­ous CRO mus­cle to the orig­i­nal late-stage tri­al sup­port­ing the OK.

Oth­er re­ac­tions ranged from cau­tious­ly op­ti­mistic to skep­ti­cal. The fi­nal, sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment on the sole pri­ma­ry end­point of ADAS-Cog12 was hit, in part, be­cause the place­bo group saw a sud­den de­cline at week 24.

None of the sec­ondary end­points were hit — echo­ing a failed Phase II pre­sent­ed in 2014. Some called the re­sults mod­est at best and mean­ing­less at worst.

Howard Fil­lit

“We have sort of in­con­sis­tent re­sults, they’re not the kind of ro­bust re­sults that I think we would want to see here in the Unit­ed States to demon­strate ef­fi­ca­cy,” Howard Fil­lit, the found­ing ex­ec­u­tive di­rec­tor and CSO of the Alzheimer’s Drug Dis­cov­ery Foun­da­tion, said in an in­ter­view with End­points News fol­low­ing the Chi­nese OK. He added: “Maybe the Chi­nese reg­u­la­to­ry agency has a dif­fer­ent kind of risk tol­er­ance and since this is a safe drug, they’re al­low­ing pa­tient ac­cess while more re­search is be­ing done.”

The way Green Val­ley’s new tri­al is de­signed, GV-971 would need to meet two met­rics to be de­clared suc­cess­ful: ADAS-cog/11 (fo­cus­ing on cog­ni­tion) and AD­CS-CG­IC (clin­i­cian’s over­all as­sess­ment of to­tal change).

Dubbed GREEN MEM­O­RY, the study will eval­u­ate a slew of oth­er end­points as well as lev­els of GV-971 in the body, and whether it af­fects brain struc­ture neu­rode­gen­er­a­tion.

So­cial im­age cred­it: Zhangjiang Hi-Tech Park

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Aduhelm OK 'bit­ter­sweet' for ALS ad­vo­cates; Con­trast­ing Covid-19 vac­cine read­outs; GSK joins TIG­IT bat­tle; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With the busiest days of June now behind us, we’re starting to think seriously about the second half of the year. In August, we have scheduled a special report where Endpoints will compile a list of the 20 most influential R&D executives in biopharma. Know a luminary who should definitely be included? Nominate them now.

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Who are the lu­mi­nar­ies dri­ving the biggest ad­vances in bio­phar­ma R&D? End­points News is ask­ing for your nom­i­na­tions for a spe­cial re­port

In biopharma, driving a drug to market is the ultimate goal — but none of that happens without a strong research and development program. At the most successful companies, those R&D efforts are spearheaded by true innovators in the field who are always looking for that next novel mechanism of action or breakthrough safety profile.

Now, Endpoints News is asking you to tell us who those guiding lights are.

Leen Kawas, Athira CEO

Biotech founder placed on leave as $400M Alzheimer's start­up idea comes un­der scruti­ny

Athira Pharma, the Alzheimer’s biotech that emerged out of obscurity last year and raised nearly $400 million for a dark-horse approach to treating neurodegeneration, has found itself in sudden turmoil.

On Tuesday evening, the company released a terse statement announcing that CEO and founder Leen Kawas had been placed on administrative leave while an independent review board investigated “actions stemming” from her doctoral research at Washington State University. Mark Litton, who joined the company as COO two years ago, will take over day-to-day operations, they said.

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Bris­tol My­ers breaks the bank on Ei­sai's fo­late re­cep­tor ADC drug, lay­ing out more than $3B+ for rights

For years, innovation in oncology has been a crapshoot with Big Pharma — the whales at the table — dropping the big bucks for the key to the next generation of tumor fighters. Bristol Myers Squibb hasn’t exactly made a name for being an innovator in the space, but that doesn’t mean it won’t splash in when it sees a potential winner.

Now, with a massive check in hand, the drugmaker is willing to put its intuition to the test.

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Michael Chambers (L) and John Ballantyne

Dana­her strikes deal to buy boom­ing next-gen man­u­fac­tur­er Alde­vron for $9.6B

Life sciences conglomerate Danaher Corp. $DHR has struck a deal to buy the fast-growing Aldevron, one of the world’s top manufacturers of hotly sought-after plasmid DNA, mRNA and recombinant proteins for the burgeoning world of vaccine and drugmakers pushing some game-changing technologies.

Buyout talks set the stage for Danaher to settle on a $9.6 billion cash pact to acquire the private Fargo, ND-based company — a key supplier for a disruptive new Covid vaccine as well as a host of gene and cell therapy and CRISPR gene editing players — founded by Michael Chambers and CSO John Ballantyne as a crew of 2 back in 1998.

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Christian Hogg, Hutchmed CEO

Hutchmed files for $600M+ IPO in Hong Kong as lead on­col­o­gy drug su­r­u­fa­tinib awaits FDA's good graces

In oncology, a flush of Chinese-developed drugs has the biopharma industry rethinking the poles of power in R&D as the blossoming nation continues to make a name for itself and pick up bundles of cash in the process. Now, as its lead drug faces a pivotal FDA review, the company formerly known as Chi-Med is planting its flag on home soil with a massive public offering.

Hutchmed — recently renamed from Chi-Med, or Hutchison China MediTech — will look to raise $603 million as part of a Hong Kong IPO that serves as a homecoming of sorts for the Chinese-based oncology player, which has listed on Nasdaq since 2016.

Jeff Albers, Blueprint CEO

Blue­print Med­i­cines nabs 4th ap­proval in bid to­ward prof­itabil­i­ty

Blueprint Medicines’ push to profitability continues.

On Wednesday, the Cambridge biotech announced the FDA approved its longtime lead drug, Ayvakit, for advanced systemic mastocytosis, a group of debilitating rare diseases where one type of immune cell — mast cells — builds up uncontrollably in a particular organ. The decision came on the heels of Phase III trials showing that more than half of late-stage patients who received the drug responded to it and did so for just over three years.

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Franz-Werner Haas, CureVac CEO (Christoph Schmidt/picture-alliance/dpa/AP Images)

UP­DAT­ED: Cure­Vac blames vari­ants as a close­ly-watched Covid vac­cine goes down in flames, fail­ing piv­otal study with woe­ful da­ta

CureVac was widely expected to come in with a late but likely late-stage winner in the race to develop new vaccines for the Covid-19 pandemic. Instead, late Wednesday, the German biotech said their mRNA candidate CVnCoV flat failed a pivotal trial — quashing any hopes for a quick entry in the blockbuster field and gutting their share price.

CVnCoV demonstrated an interim vaccine efficacy of 47% against COVID-19 disease of any severity and did not meet prespecified statistical success criteria. Initial analyses suggest age and strain dependent efficacy.

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