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.
“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.
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