Sodium Oligomannate (GV-971, trade name: Oligomannate) is a disease-modifying therapy for Alzheimer's disease developed by Green Valley Pharmaceuticals (Shanghai, China). It received conditional approval from the China National Medical Products Administration (NMPA) in November 2019 for the treatment of mild to moderate Alzheimer's disease, making it the first new disease-modifying treatment approved anywhere in the world since 2003[@xing2021][@china2019].
GV-971 is a marine-derived acidic oligosaccharide extracted from brown algae (Ascophyllum nodosum). Unlike previous Alzheimer's drugs that target [amyloid-beta](/proteins/amyloid-beta) or [tau](/proteins/tau) pathology directly, GV-971 takes a novel approach by modulating the [gut-brain axis](/entities/gut-brain-axis) through alteration of gut microbiota composition["@wang2019"].
Mechanism of Action
Gut Microbiota Modulation
GV-971 operates through a distinctive gut-brain axis mechanism:
Gut [Microbiome](/entities/microbiome) Alteration: GV-971 reduces pro-inflammatory gut bacteria (such as Escherichia/Shigella) while increasing beneficial bacteria (such as Bifidobacterium and Lactobacillus)[@wang2019]
Reduction of Peripheral Inflammation: By modulating gut microbiota, GV-971 decreases the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in the peripheral blood[@wang2019]
Neuroinflammation Reduction: Lower peripheral inflammation leads to reduced neuroinflammation in the brain through the gut-brain immune pathway[@wang2019]
Amyloid Plaque Reduction: Studies show GV-971 can reduce amyloid-beta plaque deposition in the [hippocampus](/brain-regions/hippocampus) and [cortex](/brain-regions/cortex)[@li2020]
Key Molecular Targets
Gut microbiota: Reduces Escherichia/Shigella populations
Brain [microglia](/cell-types/microglia-neuroinflammation): Modulates microglial activation states
Amyloid-beta: Reduces plaque burden in AD models
Clinical Evidence
Phase 3 Trial (Green Memory Study)
The pivotal Phase 3 trial (NCT02293915) enrolled 818 patients with mild to moderate Alzheimer's disease (MMSE score 10-26) in China[@xiao2021]:
Study Design: 36-week, randomized, double-blind, placebo-controlled
Dosage: 450 mg twice daily (900 mg total daily)
Primary Endpoint: Change from baseline in ADAS-Cog score at week 36
Results:
Significant improvement in cognitive function vs. placebo (difference: -2.15 points on ADAS-Cog at week 36, p=0.0004)
Benefits observed as early as week 4
Good safety profile with mostly mild adverse events
Supporting Studies
Phase 2 Trial: Showed dose-dependent cognitive benefits with good tolerability[@zhang2018]
Post-hoc Analyses: Suggested benefits in patients with mild to moderate AD
Real-world Data: Chinese real-world studies have reported continued use and monitoring[@green]
Dosing and Administration
Safety and Adverse Effects
Common Adverse Events
Nausea (most common)
Diarrhea
Dizziness
Headache
Fatigue
Safety Profile
GV-971 demonstrated a favorable safety profile in clinical trials:
No major organ toxicity
Low rates of serious adverse events
No significant differences in discontinuation rates vs. placebo
Drug-related adverse events were mostly mild to moderate
Regulatory Status
The FDA Fast Track designation was granted in 2020 to facilitate development and expedite review[@fda2020]. Green Valley has been conducting additional clinical trials to meet international regulatory requirements.
Comparison with Other AD Therapies
Research Pipeline
Ongoing Studies
Global Phase 3 Trials: Planning or recruiting for international trials
Combination Therapy: Studies exploring GV-971 combined with standard AD treatments
Biomarker Studies: Investigating predictive biomarkers for treatment response
Mechanism Studies: Further elucidation of gut-brain signaling pathways
Future Directions
Biomarker Development: Identifying patients most likely to respond
Combination Approaches: Testing with [cholinesterase inhibitors](/entities/cholinesterase-inhibitors) or other disease-modifying therapies
Early Intervention: Potential use in prodromal AD or preclinical populations
Mechanistic Biomarkers: Gut microbiome and inflammatory markers as treatment response predictors
See Also
[Sodium Oligomannate (GV-971) — Drug Overview](/therapeutics/sodium-oligomannate)
[Green Valley Pharmaceuticals](https://www.greenvalleypharma.com/)
[Alzheimer's Association - Drug Treatments](https://www.alz.org/alzheimers_dementia_treatments.asp)
References
[Xing XY, et al, Sodium oligomannate: a new therapeutic option for Alzheimer's disease (2021)](https://pubmed.ncbi.nlm.nih.gov/34645156/)
[Unknown, China approves GV-971, the first new drug for Alzheimer's disease in 17 years (2019)](https://doi.org/10.1136/bmj.l6570)
[Wang X, et al, Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression (2019)](https://pubmed.ncbi.nlm.nih.gov/31562858/)
[Li C, et al, GV-971 ameliorates amyloid-beta pathology and cognitive deficits in APP/PS1 transgenic mice (2020)](https://pubmed.ncbi.nlm.nih.gov/32838475/)
[Xiao S, et al, Green Memory: a phase 3 trial of GV-971 in mild-to-moderate Alzheimer's disease (2021)](https://pubmed.ncbi.nlm.nih.gov/34545857/)
[Zhang J, et al, A randomized, double-blind, placebo-controlled phase II trial of GV-971 in mild-to-moderate Alzheimer's disease (2018)](https://pubmed.ncbi.nlm.nih.gov/29339073/)
Unknown, Green Valley Pharmaceuticals - GV-971 Research (n.d.)
Unknown, FDA grants Fast Track designation for GV-971 (2020)
Pathway Diagram
The following diagram shows the key molecular relationships involving Sodium Oligomannate (GV-971) for Alzheimer's Disease discovered through SciDEX knowledge graph analysis: