On November 2, 2019, China's National Medical Products Administration (NMPA) conditionally approved Sodium Oligomannate (GV-971) as new drug for “the treatment of mild to moderate Alzheimer's disease (AD) and improving cognitive function.” Invented by Chinese scientists and invested by a Chinese company, GV-971, owning complete, independent intellectual property rights, is the first novel drug approved for AD treatment globally since 2003.

On December 29, at the Launch of GV-971 Global Strategy and 1st Gut-Brian Axis Forum, hosted by the Shanghai Institute of Materia Medica, Chinese Academy of Sciences and undertaken by Green Valley Pharmaceuticals, Yang Baofeng, Vice Chairman of the Chinese Medical Association and Academician of the Chinese Academy of Engineering, pointed out that as AD remains a conundrum for the global medical community, it’s very commendable for China to earn a place in the field, especially by securing an original achievement after no new AD drug was approved in the past 17 years.

At the event, two leading principal investigators of GV-971’s China phase III clinical study, Professor Xiao Shifu from the Center for Mental Health at Shanghai Jiao Tong University Medical College and Professor Zhang Zhenxin from Peking Union Medical College Hospital, joined IQVIA (formerly Quintiles and IMS Health, Inc.), the world’s largest CRO firm managing the China phase III clinical study, for the first time interpreted data and results of GV-971’s clinical studies in an open, systematical manner.

Led by the Center for Mental Health at Shanghai Jiao Tong University Medical College and Peking Union Hospital, the China Phase III clinical study was conducted in 34 Tier-1 hospitals across the country, involving 818 patients diagnosed with mild to moderate AD – it is also the world’s first 36-week purely placebo-controlled study in the field of AD drugs. Results showed that with 78% efficacy, GV-971 statistically improved cognitive function in patients, and was also safe and well tolerated with side effects comparable to the placebo.

For a very long time, most AD drug development focused on targeting the β-amyloid plaques that aggregate in patients' brains, which are thought to interfere with nerve signaling. But with the failure of numerous amyloid-targeting drugs in clinical studies, more and more researchers have started to explore different therapeutic strategies.

GV-971 is an orally administered mixture of acidic linear oligosaccharides derived from marine brown algae. Preclinical studies on its mechanism of action show that by reconditioning the gut microbiota, GV-971 can inhibit the abnormal increase of specific metabolites of the gut microbiota, curb peripheral and central inflammation, and reduce β-amyloid (Aβ) deposition and Tau hyperphosphorylation, thereby improving the cognitive impairment in patients. More and more international studies have proven that the gut microbiota is highly correlated with the pathogenesis of central nervous system diseases such as Parkinson’s disease, depression, and autism.

Commenting on the results, Professor David M. Holtzman and his colleagues from Washington University in St. Louis, wrote in an article published in Cell Research: “There is no question that this (mice) data further supports the emerging idea that modulation of the gut microbiome via treatments such as GV-971 or other strategies should be further explored as novel strategies to slow the progression of AD.”

Zaven Khachaturian, editor-in-chief of Alzheimer's & Dementia, the journal of the US Alzheimer's Association, noted that “Probably the most important aspect of GV-971’s approval in China is that it validates the increasing intensity of the interest in gut microbes and inflammation. Once we get insight into the mode of action, we'll be able to use that knowledge to produce, through rational drug design, more potent compounds that attack that target.”

Speaking at the event, Sue Peschin, President of the US Accelerate Cure/Treatments for Alzheimer's Disease (ACT-AD) Coalition and President & CEO of the Alliance for Aging Research, said that there was an urgent need for a life-changing treatment among AD patients and the global plan for GV-971 would create hope for tens of millions of people.

Responding to controversies and disagreements arising from the current research results, Professor Geng Meiyu, Academic Director General of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, who is GV-971’s key inventor, stated: “Our research to date has only revealed the tip of the iceberg, and there are more unknowns waiting to be tapped.” To facilitate further research, Green Valley Pharmaceuticals also announced at the event that it will invest USD 3 billion in the future to support GV-971’s post-launch real-world studies, the “Green Memory” global multi-center Phase III clinical study, studies on expansion of indications, and in-depth studies on mechanism of action.

Among these, the global multi-center Phase III clinical study will be conducted at about 200 clinical centers in geographies including North America, the European Union, Eastern Europe, and Asia Pacific. It will involve more than 2,000 mild to moderate AD patients for a 52-week double-blind study and a 26-week open-label period to further verify GV-971’s clinical value. Jeffrey Cummings, winner of the Bengt Winblad Lifetime Achievement Award (2018) from the US Alzheimer’s Association and Professor at the Cleveland Clinic Lou Ruvo Center for Brain Health will serve as the study’s leading design instructor & chief scientist – he is also the chairman of the Scientific Innovation Committee at Green Valley Pharmaceuticals.

GV-971’s global multi-center Phase III clinical study is planned for completion by 2024, as Green Valley looks forwards to securing new drug application (NDA) by 2025.

Green Valley Pharmaceuticals said: “The pathogenesis of AD is still inconclusive, and no new AD drug has been approved globally for 17 years. With extensive research, we believe that the gut-brain axis is a feasible way-out for treating AD, although this still needs further exploration.” In the future, Green Valley Pharmaceuticals will set up a special research fund based on rules of openness, equality, sharing and global operation to support outstanding scientists from around the world to participate in in-depth research on GV-971 and its mechanism of action. “By doing so, we hope to further validate the mechanism of the gut-brain axis as well as GV-971’s efficacy in an in-depth manner. It is just normal for new things to be questioned, and we are willing to work with scientists worldwide to answer today's questions with science.”

Green Valley also revealed that it will continue to work with IQVIA for the management of GV-971’s global multi-center Phase III clinical study, after the world’s largest CRO firm oversaw the drug’s China Phase III clinical study.

Link to Online References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796832/

https://www.science.org/content/article/alzheimer-s-experts-greet-china-s-surprise-approval-drug-brain-disease-hope-and-caution

https://news.cgtn.com/news/2019-12-29/China-s-first-Alzheimer-s-drug-goes-on-sale-MP5peB1r2g/index.html