Shanghai Green Valley announces NMPA approval of oligomannate for Mild to Moderate Alzheimer's Disease
Shanghai Green Valley Pharmaceuticals (Green Valley) today announced that China's National Medical Products Administration (NMPA) has approved Oligomannate (GV-971) as new drug for the treatment of "mild to moderate Alzheimer's disease (AD) and improving cognitive function."
NMPA granted Oligomannate for fast-track review in November 2018. It is the first novel drug approved for Alzheimer's disease globally since 2003. Oligomannate will provide a new treatment option to fight Alzheimer's disease for patients and is expected to be available in China by the end of 2019.
The Phase 3 clinical trial is a multicenter, randomized, double-blind, placebo-controlled, parallel-group 36 week study led by Peking Union Hospital and Shanghai Jiaotong University Medical School Mental Health Center. The study was conducted in 34 Tier-1 hospitals across China. A total of 818 patients with the diagnosis of mild to moderate Alzhemer's disease completed the study. The trial was conducted in collaboration with IQVIA (formally Quintiles) and Signant Health (formerly Bracket) among other partners.
Trial results demonstrated that Oligomannate statistically improve cognitive function in mild-to-moderate AD patients as early as week 4 and the benefit was sustained at each follow-up assessment visit. The mean difference between Oligomannate and placebo groups in ADAS-Cog12 Score (a standard cognitive measure commonly used in AD studies) was 2.54 (p< 0.0001), with sustained efficacy from first month of treatment to the end of 9 months of treatment. Oligomannate was safe and well tolerated with side effects comparable to the placebo arm.
"I have been doing research on Alzheimer's disease for 50 years, participated in multiple global multi-center studies of multiple drugs, and have never found a satisfactory treatment for Alzheimer's disease," said Professor Zhang Zhenxin, MD, a leading principal investigator of the phase 3 trial of Oligomannate and professor of Neurology at Peking Union Medical College Hospital in Beijing. "The result of the 9-month trial of Oligomannate is exciting. We finally see hope and dawn. I am sincerely happy for the patients and their families."
"There are only few drugs available to treat Alzheimer's disease, and none can delay or prevent progression of the disease," said Professor Xiao Shifu, a leading principal investigator of the phase 3 trial of Oligomannate at Center for Mental Health at Shanghai Jiaotong University Medical College. "The results of the Phase 3 clinical study showed rapid onset of efficacy of Oligomannate within 4 weeks, and that patients' cognitive function continued to improve. The treatment was safe during the 36-week clinical trial."
The cause of AD is not yet fully understood. Deposition of amyloid plaques and neurofibrillary tangles are among the proposed underlying etiologies; these are the common targets of many current investigational drugs. Oligomannate has a mechanism of action distinct from other agents currently on the market and in clinical trials. As described by Professor Geng Meiyu, the leading inventor of the drug at the Chinese Academy of Sciences Shanghai Institute of Materia Medica, the preclinical studies show that Oligomannate reconditions dysbiosis of gut microbiota, inhibits the abnormal increase of intestinal flora metabolites, modulates peripheral and central inflammation, reduces amyloid protein deposition and tau hyperphosphorylation, and improves cognitive function.
In the Research Highlight1 about the preclinical study of Oligomannate recently published in Cell Research2, Professor David M. Holtzman, chairmen of Department of Neurology and director of Hope Center for Neurological Diseases at Washington University in St. Louis and his colleagues wrote that the preclinical data "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".
Green Valley will launch Oligomannate very soon in China, and plan to submit the marketing authorization applications in selected countries following the China launch. A multi-center global phase 3 clinical trial (GREEN MEMORY) with sites in the U.S., Europe and Asia is planned to be initiated in early 2020 to support global regulatory filing of Oligomannate.
"The phase 3 clinical trial of Oligomannate conducted in China showed a sustainable cognitive benefit. It was well tolerated. This is the first new therapy for Alzheimer's disease approved in many years and we applaud this innovation," said Jeffrey Cummings, MD, Vice Chair for Research and Research Professor of UNLV Department of Brain Health and Professor and director of Center for Neurodegeneration and Translational Neuroscience Cleveland Clinic, Lou Ruvo Center for Brain Health, and a scientific advisor to Green Valley. "We look forward to the global phase 3 trial of Oligomannate to investigate its clinical effects in larger and more diverse populations and to collect samples that will provide evidence of the agent's biological effects.
"I am encouraged by the cognitive improvement, safety and tolerability associated with Oligommanate in this initial clinical trial, as well as the potential to diversify the portfolio of promising treatments for our affected patients and families," said Eric Reiman, MD, Executive Director of Banner Alzheimer's Institute and a scientific advisor to Green Valley. "I am also encouraged by the plan to further evaluate clinical and biological effects of this drug in global trials."
"The preclinical observation that Oligomannate suppresses gut dysbiosis and harnesses neuroinflammation has resulted in improvement of cognitive impairment, as evidenced by the trial results," said Philip Scheltens, MD, PhD, professor of Neurologist and CEO of Alzheimer Center Amsterdam and a scientific advisor to Green Valley. "These results advance our understanding of the mechanisms that play a role in Alzheimer's disease and implies that the gut microbiome is a valid target for development of AD therapies."