This Alzheimer’s drug has already been approved for use in China. The clinical trials that could lead to approval in the U.S. have just been abruptly canceled mid-stream.
Green Valley’s international Phase 3 trial for their seaweed-derived Alzheimer’s drug, GV-971, was unexpectedly canceled midstream due to financial challenges, according to clinical trial sites.
The international Phase 3 study of Green Valley Pharmaceuticals’ seaweed-based Alzheimer’s drug has been abruptly halted. According to multiple clinical trial sites, the cancellation is due to financial issues imposed by the COVID-19 pandemic as well as supply chain issues.
The drug — oligomannate or GV-971 — was conditionally approved in China in 2019. Eric Reiman, a former scientific advisor to Green Valley and executive director of the Banner Alzheimer’s Institute told Being Patient that he was “extremely disappointed to learn that the trial was discontinued,” adding that it was stopped “due to unexpected financial challenges related to the COVID-19 pandemic in China.”
The study, which started in October of 2020, expected to enroll 2,046 people with mild to moderate Alzheimer’s at 154 clinical trial centers across 10 different countries and regions. At that time, the company had estimated that they could finish the trial and work on submitting an application to the Food and Drug Administration for approval by 2025.
“It was a disappointment to our team when this trial was terminated,” said Jeff Pohlig, the CEO of Charter Research, an Alzheimer’s-focused drug trial center in Florida that was testing GV-971. He added that because the drug has shown promise in its Phase 3 clinical trial in China, he hopes Green Valley will restart and continue the study in the future.
Not everyone was impressed with the early trial data. Some experts expressed skepticism over the drug’s approach, its early efficacy and safety data, and the drug company themselves, spurring from a 2008 dispute in which Green Valley ran into regulatory trouble for marketing a fungus-based treatment for cancer without sufficient evidence, resulting in lawsuits and some bad press in China.
But considering the drug’s unique target — and the deep need for effective Alzheimer’s treatments — many are not ready to write the ‘seaweed drug’ off.
“Speaking as someone who is no longer affiliated with Green Valley but who is keenly interested in the development of effective [Alzheimer’s] treatments,” Reiman said, “I would still be interested in seeing the drug put to the test in a rigorous global trial.”
What is oligomannate and how does it work?
Green Valley’s seaweed-based drug is the first microbiome-based therapeutic developed for Alzheimer’s disease. Oligomannate is extracted from a mixture of seaweed and kelp, providing food for the community of bacteria living in the gut.
By targeting gut microbes, it is thought that the drug can treat cognitive impairment by way of reducing inflammation in the body and brain. It is akin to introducing more native flowers for pollinators in a forest; this one small change can make the ecosystem a little healthier.
The approach is in line with mounting research showing that treatments for Alzheimer’s and cognitive impairment could stem from the gut: Studies have shown that changing the bacteria living in the gut can impact cognition, and, according to mice studies, even potentially reverse some cognitive aging.
Oligomannate was first conditionally approved in China in 2019, pending continuous safety trials. By 2020, Green Valley received approval from the Food and Drug Administration to test it in the U.S. In the Phase 3 trial conducted in China, the drug slowed cognitive impairment when compared to a placebo control group.
Are the results convincing?
To some, the approach sounded promising even if the company had scandals in its past. But when it came to early trial results on efficacy and safety, the data was so encouraging, it began to draw scrutiny — and some amount of skepticism — from Alzheimer’s drug experts.
Dr. Lon Schneider, professor at the University of Southern California Keck School of Medicine, noted that the rate of adverse effects was “remarkably” low. Schneider commented on the study for AlzForum:
“Patients for this study were not allowed to take cholinesterase inhibitors, and as has been demonstrated in U.S. samples, the differences in clinical characteristics and course between those taking cholinesterase inhibitors and those not taking them may affect outcomes.”
Others noted that the Chinese approval of the drug came as a surprise to many scientists.
Yi Rao, neurobiologist and president of Capital Medical University in Beijing, published criticism in Cell Research questioning the underlying mechanism based on previous studies of the drug. In the article, he wrote: “I have never come across a single drug with so many targets for curing or alleviating one disease.”
Rao responded to Being Patient’s request for comment via email, stating that: “It was widely suspected that GV-971 was a fraud.”
What’s next for oligomannate?
Green Valley did not issue an official statement explaining the halt to the Phase 3 clinical trials.
Given the preliminary results and safety profile, Reiman hopes that the drug has another chance at clinical trials. Asked if it was normal for companies to run out of financing during an ongoing clinical trial, Reiman said “it’s extremely uncommon and was unexpected.”
As of this writing, Green Valley has not responded to a request for comment via email.
“My heart goes out to the research participants and their families, the trial site personnel, and others involved in the study,” Reiman said. “Alzheimer’s disease takes a terrible toll on our patients and families, and we need to find better ways to address their needs.”