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

Biogen CEO Michel Vounatsos (via Getty Images)

With ad­u­canum­ab caught on a cliff, Bio­gen’s Michel Vounatsos bets bil­lions on an­oth­er high-risk neu­ro play

With its FDA pitch on the Alzheimer’s drug aducanumab hanging perilously close to disaster, Biogen is rolling the dice on a $3.1 billion deal that brings in commercial rights to one of the other spotlight neuro drugs in late-stage development — after it already failed its first Phase III.

The big biotech has turned to Sage Therapeutics for its latest deal, close to a year after the crushing failure of Sage-217, now dubbed zuranolone, in the MOUNTAIN study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

Pascal Soriot (AP Images)

As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

Endpoints Premium

Premium subscription required

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

Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

Af­ter Ko­dak de­ba­cle, US lends $1.1B to a syn­thet­ic bi­ol­o­gy com­pa­ny and their big Covid-19, mR­NA plans

In mid-August, as Kodak’s $765 million government-backed push into drug manufacturing slowly fell apart in national headlines, Ginkgo Bioworks CEO Jason Kelly got a message from his company’s government liaison: HHS wanted to know if they, too, might want a loan.

The government’s decision to lend Kodak three quarters of a billion dollars raised eyebrows because Kodak had never made drugs before. But Ginkgo, while not a manufacturing company, had spent the last decade refining new ways to produce materials inside cells and building automated facilities across Boston.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

Chi­na opens the door for biotech in­vestors in Hong Kong to buy Shang­hai stocks, and vice ver­sa

When Shanghai’s STAR board began opening its doors to biotech, it was considered not just a rival to Nasdaq but also the stock exchange in Hong Kong. Those perceptions may take an amicable turn as China expands a mutual access program with the city.

The changes mean investors in mainland China will be able to own Hong Kong biotech chapter stocks, while those in Hong Kong — a much more internationally connected group — would have access to those listed on STAR. In effect, it turns the Shanghai market into a globally accessible exchange overnight while also broadening a key source of revenue for HKEX.

Vivek Ramaswamy (Jeff Rumans/JPM 2020)

Urovan­t's lead drug dis­ap­points in mid-stage study as first big FDA de­ci­sion looms

Just as Urovant gets ready for its first big FDA decision on vibegron, the drug has flopped in what would’ve been a follow-on indication.

In a Phase IIa trial involving women with abdominal pain due to irritable bowel syndrome, vibegron failed to meet the bar on improving “average worst abdominal pain” over 12 weeks, compared to placebo, among IBS-D patients.

There were actually slightly more responders in the placebo group than in the drug arm, with only 40.9% of those randomized to vigebron achieving at least a 30% decrease in “worst abdominal pain” in the past 24 hours. The trial enrolled 222 women but only 189 completed the study.

Gen­mab ax­es an ADC de­vel­op­ment pro­gram af­ter the da­ta fail to im­press

Genmab $GMAB has opted to ax one of its antibody-drug conjugates after watching it flop in the clinic.

The Danish biotech reported Tuesday that it decided to kill their program for enapotamab vedotin after the data gathered from expansion cohorts failed to measure up. According to the company:

While enapotamab vedotin has shown some evidence of clinical activity, this was not optimized by different dose schedules and/or predictive biomarkers. Accordingly, the data from the expansion cohorts did not meet Genmab’s stringent criteria for proof-of-concept.

Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

Vas Narasimhan's 'Wild Card' drugs: No­var­tis CEO high­lights po­ten­tial jack­pots, as well as late-stage stars, in R&D pre­sen­ta­tion

Novartis is always one of the industry’s biggest R&D spenders. As they often do toward the end of each year, company execs are highlighting the drugs they expect will most likely be winners in 2021.

And they’re also dreaming about some potential big-time lottery tickets.

As part of its annual investor presentation Tuesday, where the company allows investors and analysts to virtually schmooze with the bigwigs, Novartis CEO Vas Narasimhan will outline what he thinks are the pharma’s “Wild Cards.” The slate of five experimental drugs are those that Novartis hopes can be high-risk, high-reward entrants into the market over the next half-decade or so, and cover a wide range of indications.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

Endpoints Premium

Premium subscription required

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