A Greater China investigator meeting was recently held for the global multi-center Phase III clinical trial of GV-971 (Sodium Oligomannate), China’s novel drug for treating Alzheimer’s disease (AD). The meeting announced the official commencement of GV-971 global clinical trial in Greater China, symbolized by the completion of site initiation visit (SIV) at Xuanwu Hospital of Capital Medical University, the trial’s first clinical site in China, on May 20. To date, GV-971’s Phase III global trial has already initiated 72 clinical sites in the US and Canada, completed screening of 334 patients, and randomly enrolled 72 of them, all of whom are now receiving drug treatment.

The meeting was hosted by IQVIA, the world-famous CRO now managing GV-971 global clinical trial, and was attended by more than 200 clinical investigators either onsite or online.

“We expect 40% of the enrolled patients will come from Greater China.” Dana Cain from IQVIA, who is responsible for managing GV-971 global Phase III clinical trial, noted that IQVIA’s close partnerships with a number of top-class suppliers in the global clinical field will help provide high-quality trial data and ensure consistency across all clinical sites. In addition, IQVIA will strictly follow US FDA’s requirements to conduct on-site training on measurements such as scale, electrocardiogram, and imaging during SIVs, to ensure the trial’s rigor to the greatest extent.

GV-971’s 52-week double-blind global trial is planned for completion by 2025, to be followed by new drug application (NDA) in Europe and the US. While the trial is designed by a global expert team headed by renowned AD expert Jeffrey Cummings, Green Valley Pharmaceuticals will continue to work with IQVIA for clinical trial operation and management.

“GV-971 China Phase III clinical trial is a 9-month (36-week) randomized, double-blind, placebo-controlled trial. We found that from the fourth week, the drug significantly improved cognitive function in our patients. During the entire 9-month trial, the drug demonstrated sustained efficacy in steady cognitive improvement. Building on experiences gained from the China clinical trial, the current global multi-center clinical trial has been designed to be a 52-week randomized, double-blind, placebo-controlled trial, plus a 26-week extended period. The global trial will increase the proportion of patients with moderate-to-severe AD, and include new endpoints such as biomarkers and microbiota related to the disease course, including immunity, metabolism, and nerve damage in the blood. Therefore, we aim to further clarify GV-971’s potential in changing AD’s disease course, and further understand its long-term therapeutic effects through the trial.” Noted Professor Xiao Shifu from Shanghai Mental Health Center, who is also the national coordinating investigator of GV-971’s global multi-center Phase III clinical trial in China, at the conference.

As GV-971’s key inventors, Professor Geng Meiyu, Academic Director of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Dean of the Green Valley Research Institute, commented, “Using GV-971 as a probe, we discovered that AD is a complex systemic disease of multi-system disorder and multi-organ aging. In our research, we found that gut microbiota dysbiosis can lead to peripheral inflammation, and when these inflammatory immune cells eventually infiltrate the brain, they will lead to neuroinflammation and in turn accelerate β-amyloid (Aβ) deposition and Tau hyperphosphorylation in AD’s disease course. Ultimately, this results in loss of neurons and impairs cognitive functions.”

Professor Geng added that the common pathological mechanism of gut microbiota provides a very important platform and opportunity for the multi-purpose application of carbohydrate drugs. “While launching our global clinical trial, the research team is also actively conducting new theoretical explorations and pursuing breakthroughs in new indications for GV-971. Based on the gut-brain axis and using imbalanced immune functions and metabolic disorders as an important bridge, the research team has re-verified whether GV-971 can simultaneously treat diseases that share the common pathological mechanism with AD, such as PD (Parkinson's disease) and VD (vascular dementia), namely complex diseases that relate to autoimmune diseases caused by the gut-brain connection.”

To date, the pre-clinical trial of GV-971 on PD has been basically completed, and the application for a global multi-center Phase II clinical trial will be submitted in the second half of 2021. At the same time, the preclinical studies for three new indications, VD, NMO (neuromyelitis optica) and ALS (amyotrophic lateral sclerosis), are currently underway, while the application for a clinical trial for GV-971’s effects on NMO is expected for submission by the end of 2021.