Toward the end of last year, TrialSite News introduced the first approved Alzheimer’s disease (AD) drug approved in years; Chinese regulators approved the drug Oligomannate (GV-971) made by Green Valley Pharmaceuticals. They made good on their promise to hit America next. On April 8, 2020, the U.S. Food and Drug Administration (FDA) gave a formal nod to the Chinese company’s Investigational New Drug (IND) application, meaning that they could commence a Phase III clinical trial in the United States to test the drug on patients with AD. According to the company’s internal planning timeline, the ultimately Phase III clinical trial is planned to be completed in 2025 and a new drug application (NDA) submission expected by 2025. In a period of disappointment for most commercial clinical sponsors targeting AD, Green Valley Pharmaceuticals has a shot now at the world’s largest market.
The Premise of this Drug: The Gut
There is a growing body of evidence revealing that gut microbiota is highly correlated with the incidence of Parkinson’s disease, depression, autism, and other central nervous system diseases. GV-971 obtained conditional approval from China’s National Medical Products Administration (NMPA) for improving the cognitive function of patients living with mild to moderate Alzheimer’s disease back in November 2019; the company launched the product on December 29, 2019.
FDA Basis for Approval
The FDA approved the IND calling for a Phase III international multi-center Phase III clinical trial based on the full data package of GV-971 nonclinical, clinical, chemistry, manufacturing and control (CMC) as well as the Phase III clinical efficacy and safety outcomes generated by the Chinese Phase III trial. Hence, the Chinese industry sponsor can skip Phases I and II—directly proceeding to a comprehensive international Phase III clinical trial.
What is GV-971?
The drug, an orally administered mixture of linear oligosaccharides derived from marine brown algae, during preclinical studies revealed it can improve cognitive function by reshaping the balance of gastrointestinal microbiota, inhibiting the abnormal increase of specific metabolites of this gut microbiota, inhibiting the abnormal increase of specific metabolites of this gut microbiota, reducing peripheral and central inflammation, β-amyloid deposition and hyperphosphorylation of Tau protein.
Green Valley has been collaborating with the world’s largest contract research organization (CRO) IQVIA (formerly Quintiles) for clinical operation to manage the large Phase III study.
Led by IQVIA, this study will involve over 2,000 patients with mild to moderate AD. Comprised of a 12-month double-blind treatment period and a 6-month open-label period, the study will be conducted by 200 sites in North America, Europe and Asia-Pacific regions including China.
Key Opinion Leader drives study design
Jeffrey Cummings, professor of Neurotherapeutics and Drug Development in the Neurological Institute, Cleveland Clinic—and winner of the Bengt Winblad Lifetime Achievement Award (2018) from National Alzheimer’s Association of America has been leading the clinical trial design and is positioned to serve as the Chairman of the Scientific Innovation Committee (SIC) for Green Valley.
The principal investigators (PIs) that have been selected for the Phase III clinical trial include:
Martin Farlow, MD Professor, Indiana University School of Medicine
Roy Jones, Professor University of Bristol
Bruno Vellas, Chair of the Toulouse Gerontopole, Head of the Department of Internal Medicine and Geriatrics at Toulouse University Hospital, Head of the Alzheimer’s Disease Clinical Research Centre, University of Toulouse
China PI’s include:
Jia Jianping, Professor Xuanwu Hospital of Capital Medical University
Xiao Shifu, Professor, Shanghai Mental Health Center
Call to Action: If this trial goes well, there isn’t any projected approval date until 2024 to 2025 but given there isn’t anything close to this range in the North American or European AD drug development pipelines, this is significant. Sign up for the daily newsletter for updates.