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Name: GV-971
Synonyms: sodium oligomannate, sodium oligo-mannurarate
Therapy Type: Small Molecule (timeline)
Target Type: Amyloid-Related (timeline), Inflammation (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Inactive)
Status in Select Countries: Approved in China
Company: Shanghai Green Valley Pharmaceuticals


This mixture of acidic linear oligosaccharides is derived from brown algae. The mechanism of action of the preparation remains unclear, although several different mechanisms have been proposed by the same research group between 2003 and 2013. Among those are a report that algae-derived acidic oligosaccharides de-aggregate Aβ (Hu et al,., 2004; Jiang et al., 2021), one that they prevent astrocyte-mediated inflammatory responses to amyloid plaques (Wang et al., 2007), and one that they bind to many proteins inside neurons (Liu et al., 2009).

The most recent preclinical study concerns an effect via alteration of intestinal bacteria (Wang et al., 2019). In this study, the gut microflora in 5XFAD and APP/PS1 AD mice facilitated peripheral immune cell entry into the brain, microglia activation, and disease progression, and treatment with GV-971 was reported to restore the gut microbial profile to normal and to lessen brain immune cell infiltration and inflammation. GV-971 reportedly also reduced brain Aβ burden, tau hyperphosphorylation, and cognitive deficits in these mice.

This paper was subsequently challenged as a matter arising in the same journal (Rao, 2020) and on the online journal club website PubPeer. According to news sources, a scientific integrity board in China investigated five papers on GV-971. In 2020, the panel issued a formal criticism of the lead scientist, Geng Meiyu, for misuse of graphics, but charged no fraud (news story, Feb 2021 Science news).


According to the company, Green Valley completed a Phase 1 study in 112 normal people in 2008, though no information on this trial appears in  

In October 2011, the company launched a Phase 2 trial at multiple sites in China, enrolling 255 people with mild to moderate AD who were not receiving treatment with any other AD drugs. They received 600 or 900 mg of GV-971 per day or placebo for six months. The primary endpoint was the change in ADAS-Cog12; secondary endpoints include changes on the Clinician’s Impression of Change-plus (CIBIC-plus), activities of daily living (ADL), and neuropsychiatric inventory (NPI). According to results presented at the 2014 CTAD conference, the trial failed to meet its primary endpoint, with no slowing of decline on the ADAS-cog in the treated group. The 900 mg dose was reported to slow decline on the CIBIC-plus compared with placebo (see Derek Lowe commentary). In September 2020, results of this trial were published, including an FDG-Pet substudy with 25 patients (Wang et al., 2020). Glucose metabolism declined less in some brain regions in the 900 mg treatment than placebo group, but the differences fell short of statistical significance.

In April 2014, Green Valley started a Phase 3 trial at 34 sites in China. In the study, 818 people with clinically diagnosed mild to moderate AD were randomized to 900 mg drug per day or placebo for nine months. Participants were not allowed to take acetyl cholinesterase inhibitors or namenda during the study. No amyloid or tau biomarkers were used. Again, the primary outcome was change on ADAS-Cog; secondary outcomes were the same as in Phase 2, with the addition of FDG-PET. As reported at CTAD 2018, this trial reached its primary endpoint, with the treatment group posting higher ADAS-Cog scores than placebo at four, 12, 24, and 36 weeks. There was a trend toward improvement on the CIBIC, but no change in any other secondary outcomes (Nov 2018 conference news). A subgroup analysis suggested drug effects were larger in people with lower MMSE scores at the start of the trial. GV-971 was well-tolerated. Eighty percent of participants completed the trial, and rates of adverse events were similar between treatment and placebo groups. Results were published after peer review (Xiao et al., 2021).

On November 2, 2019, Green Valley announced that the drug had received conditional marketing approval in China to improve cognitive function in mild to moderate AD (see press release). The drug began selling in China in December 2019. The company expected full approval in early 2020, pending the submission of animal safety data (Nov 2019 news and commentary).

In October 2020, Green Valley began a global Phase 3 trial called Green Memory. It was to enroll 2,046 people with mild to moderate AD and randomize them to GV-971 or placebo for one year, followed by six months of open-label GV-971 for all participants. Like prior trials of this oligomannate preparation, this study also does not allow concomitant use of standard FDA-approved AD medications. Primary endpoints were to be the ADAS-Cog11 and ADCS-Clinical Global Impression of Change; secondary endpoints were to include other clinical and psychiatric measures, as well as measures of health care usage and burden. The registration also lists blood pharmacokinetics and MRI as additional outcomes. According to a November 2020 presentation at the CTAD conference, the trial was to include biomarker outcomes of blood Aβ, phospho-tau, neurofilament light, inflammation, and microbiome status, plus fecal microbiome analysis. The company had announced it would conduct the trial at 200 sites in North America, Europe, and Asia-Pacific regions (Apr 2020 press release), and as of May 2021, 65 sites across the United States and Canada were listed as recruiting. The study was expected to run through 2025.

According to, the investigators completed a second Phase 1 study in China, testing bioavailability of different capsule formulations in healthy adults. Another Phase 1 study, also in China, began recruiting in October 2018 to assess safety and pharmacokinetics of higher doses up to 1,500 mg; the status of that trial is unknown.

In June 2021, the company began a post-marketing study to evaluate the long-term safety of 900 mg/day GV-971 in China. It will monitor 2,500 patients who are prescribed the drug for nearly two years for adverse events, withdrawal from the study, as well as vital signs, laboratory tests, and electrocardiograms. An additional post-marketing study began in December 2021 enrolling 800 patients to assess the long-term effects on cognition. The primary outcome of this study is change in ADAS-Cog11 after one year, with secondary outcomes of change at two years, as well as change in MMSE, ADCS-ADL, and adverse events. The study is recruiting at two sites in China.

In November 2021, a trial was registered to compare GV-971 to the cholinesterase inhibitor donepezil in 150 patients with mild to moderate Alzheimer’s disease. The study, at a single hospital in China, will compare donepezil 5 mg daily, GV-971 900 mg, or the combination, against a primary outcome of change in ADAS-Cog after 36 weeks. The study is slated to run from December 2021 to December 2024. A separate, similar combination trial began in July 2021 at a different university in China (see WHO registry). This study will enroll 120 patients in four arms (GV-971, donepezil, both, or placebo), and use the CDR overall score as a primary outcome. It is expected to run through 2024.

In January 2022, Green Valley announced that the U.S. FDA would allow a trial in people with early stage Parkinson’s disease (press release). The company is planning a 36-week study in 300 patients in North America and the Asia Pacific region. No trial was registered as of April 2022.

In May 2022, the global Phase 3 Green Memory trial was terminated early due to financing problems and complications of the COVID pandemic in China. As of April 26, 1308 prospective participants had been screened; 439 were randomized, and the trial had passed an initial DSMB assessment. North American sites had enrolled 257, European sites 118, Chinese sites 64 patients. Research and marketing of GV-971 will continue in China, according to the company (see press release). 

For details, see

Last Updated: 16 May 2022


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News Citations

  1. Fits and Starts: Trial Results from the CTAD Conference
  2. China Approves Seaweed Sugar as First New Alzheimer’s Drug in 17 Years

Therapeutics Citations

  1. Donepezil

Paper Citations

  1. . A phase II randomized trial of sodium oligomannate in Alzheimer's dementia. Alzheimers Res Ther. 2020 Sep 14;12(1):110. PubMed.
  2. . A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia. Alzheimers Res Ther. 2021 Mar 17;13(1):62. PubMed.
  3. . Acidic oligosaccharide sugar chain, a marine-derived acidic oligosaccharide, inhibits the cytotoxicity and aggregation of amyloid beta protein. J Pharmacol Sci. 2004 Jun;95(2):248-55. PubMed.
  4. . Molecular Insights into the Inhibitory Effect of GV971 Components Derived from Marine Acidic Oligosaccharides against the Conformational Transition of Aβ42 Monomers. ACS Chem Neurosci. 2021 Oct 6;12(19):3772-3784. Epub 2021 Sep 27 PubMed.
  5. . A marine-derived acidic oligosaccharide sugar chain specifically inhibits neuronal cell injury mediated by beta-amyloid-induced astrocyte activation in vitro. Neurol Res. 2007 Jan;29(1):96-102. PubMed.
  6. . Identification of AOSC-binding proteins in neurons. Chinese Journal of Oceanology and Limnology. 23 January 2009
  7. . Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression. Cell Res. 2019 Oct;29(10):787-803. Epub 2019 Sep 6 PubMed.
  8. . Omission of previous publications by an author should be corrected. Cell Res. 2020 Sep;30(9):819. PubMed.

External Citations

  1. Derek Lowe commentary
  2. press release
  3. Apr 2020 press release
  4. WHO registry
  5. press release
  6. press release
  8. PubPeer
  9. news story
  10. Feb 2021 Science news

Further Reading


  1. . The microbiome: A target for Alzheimer disease?. Cell Res. 2019 Oct;29(10):779-780. PubMed.
  2. . Hypothesis: Does the Apparent Protective Action of Green Valley's Drug GV971 Against Cognitive Decline Result from Antiviral Action Against Herpes Simplex Virus Type 1 in Brain?. J Alzheimers Dis. 2020;76(1):85-87. PubMed.
  3. . Pharmacological Strategies to Improve Dendritic Spines in Alzheimer's Disease. J Alzheimers Dis. 2020 Dec 2; PubMed.
  4. . Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer's Disease. Pharmaceuticals (Basel). 2020 Sep 11;13(9) PubMed.
  5. . Sodium Oligomannate: First Approval. Drugs. 2020 Mar;80(4):441-444. PubMed.
  6. . Modifying the diet and gut microbiota to prevent and manage neurodegenerative diseases. Rev Neurosci. 2022 Mar 21; PubMed.

External Resources

  1. Alzheimer’s experts greet China’s surprise approval of a drug for brain disease with hope and caution
  2. Identification of AOSC-binding proteins in neurons