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[1][2].
GV-971 is a marine-derived acidic oligosaccharide extracted from brown algae (Ascophyllum nodosum). Unlike previous Alzheimer's drugs that target amyloid-beta or tau pathology directly, GV-971 takes a novel approach by modulating the gut-brain axis through alteration of gut microbiota composition[3].
GV-971 operates through a distinctive gut-brain axis mechanism:
Gut Microbiome Alteration: GV-971 reduces pro-inflammatory gut bacteria (such as Escherichia/Shigella) while increasing beneficial bacteria (such as Bifidobacterium and Lactobacillus)[3:1]
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[3:2]
Neuroinflammation Reduction: Lower peripheral inflammation leads to reduced neuroinflammation in the brain through the gut-brain immune pathway[3:3]
Amyloid Plaque Reduction: Studies show GV-971 can reduce amyloid-beta plaque deposition in the hippocampus and cortex[4]
The pivotal Phase 3 trial (NCT02293915) enrolled 818 patients with mild to moderate Alzheimer's disease (MMSE score 10-26) in China[5]:
Results:
| Parameter | Details |
|---|---|
| Dosage | 450 mg twice daily (900 mg total daily) |
| Route | Oral |
| Formulation | Capsule |
| Duration | Chronic, long-term treatment |
| Food Interaction | Take with or without food |
GV-971 demonstrated a favorable safety profile in clinical trials:
| Region | Status | Year |
|---|---|---|
| China (NMPA) | Approved (conditional) | 2019 |
| US (FDA) | Fast Track Designation | 2020 |
| US (FDA) | Phase 3 planned | Ongoing |
| EU (EMA) | Not yet filed | — |
The FDA Fast Track designation was granted in 2020 to facilitate development and expedite review[8]. Green Valley has been conducting additional clinical trials to meet international regulatory requirements.
| Feature | GV-971 | Donepezil | Memantine | Aducanumab |
|---|---|---|---|---|
| Target | Gut-brain axis | Cholinesterase | NMDA receptor | Amyloid-beta |
| Type | Disease-modifying | Symptomatic | Symptomatic | Disease-modifying |
| Route | Oral | Oral | Oral | IV infusion |
| Approval | China | Worldwide | Worldwide | US only |
| Mechanism | Microbiome modulation | Acetylcholinesterase inhibition | NMDA modulation | Amyloid clearance |
Xing XY, et al. Sodium oligomannate: a new therapeutic option for Alzheimer's disease. Neurosci Bull. 2021. ↩︎
China approves GV-971, the first new drug for Alzheimer's disease in 17 years. BMJ. 2019. ↩︎
Wang X, et al. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression. Cell Discov. 2019. ↩︎ ↩︎ ↩︎ ↩︎
Li C, et al. GV-971 ameliorates amyloid-beta pathology and cognitive deficits in APP/PS1 transgenic mice. Acta Pharmacol Sin. 2020. ↩︎
Xiao S, et al. Green Memory: a phase 3 trial of GV-971 in mild-to-moderate Alzheimer's disease. Innovation (Camb). 2021. ↩︎
Zhang J, et al. A randomized, double-blind, placebo-controlled phase II trial of GV-971 in mild-to-moderate Alzheimer's disease. J Alzheimers Dis. 2018. ↩︎