Is the world ready for GV-971(Oligomannate)? Because the first new approved Alzheimer’s drug in many years is coming to a clinical trial near you. Conditionally approved by China’s regulators, many in the West are skeptical. However, industry sponsor Green Valley Pharmaceutical Co. Ltd. moves into full throttle worldwide. Confidence is soaring and the momentum is building. But there are skeptics.
Starting in 2020, the New Decade, a Chinese-created breakthrough drug will undergo trials in the West and elsewhere. GV-971, an orally administered drug, will be tested in 200 clinical sites from North America and the European Union to Eastern Europe, Asia Pacific, and other regions reports Xinhua.
Post successful animal studies, over 1,100 Chinse Alzheimer’s disease patients participated in clinical trials leading up to the Chinese regulatory approval. In the final study, 818 participants from 34 leading Chinese hospitals tested 450mg GV-971 orally two times per day for 9 months duration. The results, according to the Chinese press: a safe and effective improvement in cognition. The Chinese-based studies were led by prominent academic medical centers, including Peking Union Hospital and Shanghai Jiaotong University Medical School Mental Health Center.
Who was the Principal Investigator?
The lead investigator for the GV-971 (Oliogomannate) Phase III trial was Professor Zhang Zhenxin, MD, and professor of Neurology at Peking Union Medical College Hospital in Beijing. The Chinese press has quoted Professor Zhang, saying, “I have been doing research on Alzheimer’s disease for 50 years, participated in multiple global multi-center studies on multiple drugs, and have never found a satisfactory treatment for Alzheimer’s disease.” He continued, “The result of the 9-month trial of Oligomannate is exciting. We finally see hope and down. I am sincerely happy for patients and their families.”
Professor Zhang appears to be a heavy hitter in China, working for a prestigious institution for many years. Moreover, he has done business with Western pharma, serving as a principal investigator for Xian-Janssen Pharmaceutical Ltd., one of China’s largest pharma joint ventures with American Johnson & Johnson.
New Drug Application with FDA 2024
Ambitious and confident, sponsor Green Valley plans on submitting a New Drug Application (NDA) with the FDA by 2024 and the European Medicines Agency (EMA) by 2025. This is a big deal. If it turns out that this medicinal product actually works, then many of the estimated 5.8 million Americas living with Alzheimer’s disease will have a new and exciting option. And in the process, Green Valley will become incredibly valuable.
From a Lab via A Collaborative Effort
Starting out of the lab of Dr. Meiyu Geng of the Chinese Academy of Sciences’ Shanghai Institute of Materia Medica (a center focused on traditional Chinese medicine), GV-971’ s active ingredient is sodium oligo-mannurarate—which is derived from brown algae—essentially a seaweed. Meiyu and team have been at it for 22 years. The drug purportedly works by actually modifying gut bacteria, which was proven to reduce brain inflammation in genetically engineered mice afflicted with Alzheimer’s. Recent results were published in the international journal Cell Research in September, 2019.
West Remains Upbeat, Cautious and for Some Real Question Marks
Some researchers in America offer excitement, such as University of Nevada in Las Vegas researcher Jeffrey Cummings, who noted, “This is very exciting and important; GV-971 is the first drug approved anywhere in the world for Alzheimer’s disease since 2003.” Of course, critics will point out that Cummings “advises” the sponsor Green Valley Pharmaceutical Co. and could be considered biased. That is hogwash—not a problem. What matters is the substance of their output. Cummings does note that GV-971 wouldn’t yet meet the FDA’s approval criteria until there are significant results on two measures of cognitive ability as well as two positive Phase III clinical trials.
Sangram Sisoida, a neurobiologist at the University of Chicago who has studied the impact of the microbiome on Alzheimer’s disease, commented, “I think it’s fascinating, and if it’s true that [the effects are happening] through the microbiome, that’s fantastic.” Of course, just like China’s regulators, Sisodia would like to see more evidence as many aren’t convinced the subtle improvements observed with Alzheimer’s patients measured by the cognitive test are clinically meaningful.
Interestingly, Zaven Khachaturian, editor-in-chief of Alzheimer’s & Dementia, the Alzheimer’s Association journal, suggested, “Probably a key point of the recent approval is that “it validates the increasing intensity of the interest in gut microbes [and] inflammation.”
Skeptics have come out, however, including an important writer from Science Magazine named Derek Lowe who raised a number of concerns, including: (1) He believes that the summary of the Phase II clinical trial data failed to achieve statistical significance when comparing the drug versus placebo—which leads him to the obvious question of why or how did they let the trial progress to Phase III; (2) He noted a file making the rounds in Chinese social media revealing more information—specifically that the “GV-971 group had significantly greater improvement on the ADAS-Cog12 at every time point compared to placebo control” in a graph with a subtitle “Primary Outcome: Full Analysis Set.” The depiction presents some strange anomalies that Lowe would like further elaboration on, not to mention more substantive data for the Phase III trial; (3) Lowe notes that the drug’s commercial sponsor, Green Valley, has faced regulatory troubles in the past—notably back in 2007 and onward where, among other things, it appears the company could have been associated with questionable claims about curing cancer, which attracted law enforcement attention in China. Finding any news content back then in English is difficult to impossible; and (4) Lowe’s scrutiny of research papers out of Meiyu Geng’s laboratory led him to identify issues concerning accuracy and fidelity of certain work product.
Consequently, Lowe reports, “I am even less thrilled than I was yesterday about the prospects for this new drug.”
Green Valley Profile
This company, Green Valley Pharmaceuticals (Green Valley Pharma) is actually shrouded in a little mystery. They don’t highlight their executive leadership or mention their investors like most biopharmaceutical companies.
We do know they were founded in 1997 and are based in the Zhangjiang Science City Shanghai. Led by 100+ researchers and scientists they employ a total of approximately 1500. Their focus is “advanced carbohydrate drug R&D technology,” and they control two manufacturing sites in China, including one in Shanghai and another in Liaoning Province. Their breakthrough Alzheimer’s drug, Oliogomannate, was approved by the Chinese regulatory authority in late 2019. They have set up a U.S. operation based in the Arizona led by Chicago-based Jinhe Li, PhD, according to their website.
Strong Government Ties
Moreover, we know they are among the pride of the science and technology hub of Zhangjiang National Innovation Demonstration Zone, which is among many regionally planned science and technology parks competing in provinces across China. This particular center is run by Shanghai’s Mayor according to its organizational structure. It would appear, according to Chinese press, that Green Valley Pharma is part of the Shanghai Green Valley (Group) Co Ltd, an innovation-driven medical investment group bringing together Western-focused drug development R&D with traditional Chinese medicine.
Apparently, they also have a “Green Valley Research Institute” established to set up R&D centers in Beijing, Benxi and Liaoning province not to mention Changchun of Jilin province. The biotech Green Valley Pharma was formed in partnership with the Shanghai Institute of Materia Medica under the Chinese Academy of Sciences (CAS) ultimately offering scientific and research assets not to mention facilities, etc.
Hence, Green Valley itself (at least in its latest form) is backed by a government back entity—CAS—the national “think tank” and governing academic body for China. The world’s largest research organization, comprising of about 60,000 researchers working in 114 institutes, this governmental entity has created hundreds of commercial enterprises, including Lenovo while ranking has one of the top research organizations in the world.
TrialSite News research concludes that given China’s global push to be a nexus for R&D and drug development, the Chinese government, at least indirectly, has considerable investment and emphasis on this most recent approval. Still an experimental product in the West, if it performs in clinical trials there, than the news is really big, and perhaps millions struggling with Alzheimer’s can improve their quality of life. This would be fantastic. The returns for those Chinese investors in Green Valley, whoever and wherever they are, will be great as well.