Nine Phase One (mannote sodium) / Shanghai Greenvalley - LARVOL DELTA

Sodium oligomannate modulates the gut-brain axis to alleviate post-stroke cognitive impairment by restoring butyrate metabolism. (PubMed, Microbiome) - "Intestinal butyrate levels are significantly associated with PSCI. GV-971 mitigates post-stroke cognitive decline by modulating the gut microbiota to increase butyrate production, highlighting its potential as a therapeutic agent for PSCI."

Journal • Alzheimer's Disease • Cardiovascular • Cognitive Disorders • Inflammation • Transplantation • HDAC3

Efficacy of mannate sodium (GV-971) in the treatment of behavioral and psychological symptoms of in patients with mild to moderate Alzheimer's disease (ChiCTR) - P=N/A | N=120 | Not yet recruiting | Sponsor: The Fourth People's Hospital of Chengdu; The Fourth People's Hospital of Chengdu

New trial • Alzheimer's Disease • CNS Disorders

The Role of Lipoprotein and Gut Microbiome in Alzheimer's Disease: A Review of Novel Findings and Potential Applications. (PubMed, Curr Alzheimer Res) - "Novel therapies targeting lipoproteins, such as ALZ-801 and IDOL inhibitors, show promise in preclinical and clinical trials...Interventions, like probiotics, GV-971, and polyphenols, demonstrate efficacy in restoring microbial balance and mitigating cognitive decline...Integrating insights into lipoprotein biology and gut microbiota dynamics may offer transformative potential for AD treatment, emphasizing combinatorial approaches to modulate these interconnected pathways. Further research is warranted to elucidate mechanistic links and translate preclinical findings into clinical applications."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • Metabolic Disorders • APOE

Study on the improvement of cognitive deficits in APP/PS1 mice by danggui shaoyao san and its disassembled prescriptions through modulation of the gut microbiota. (PubMed, Front Microbiol) - "Forty APP/PS1 and eight C57BL/6 mice were divided into six groups: DSS (6.4 g/kg/d), QDW (4.6 g/kg/d), DW (1.8 g/kg/d), GV971 (positive control, 40 mg/kg/d), model (saline), and control (saline)...Danggui Shaoyao San and its disassembled prescriptions ameliorate AD-related cognitive impairment and gut dysbiosis, enhance microbial diversity, and modulate metabolic pathways, supporting their therapeutic potential via gut-brain axis regulation. This study elucidates the multi-target mechanisms of DSS in AD treatment, advancing TCM rationalization for neurodegenerative disorders."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Mood Disorders • Psychiatry

Chinese authorities did not renew a conditional approval of Green Valley Pharmaceuticals’ controversial Alzheimer’s disease drug sodium oligomannate, also known as GV-971... (Fierce Pharma) - "As part of its routine disclosure of regulatory activities on Aug. 12, China’s National Medical Products Administration (NMPA) put its responses to Green Valley’s applications to turn GV-971’s conditional nod into a full approval in a group marked 'notification delivery' but not the 'approval document delivery' list. This move suggests that the drug did not get approval....The exact reason for the rejection is unclear."

China approval • Alzheimer's Disease

Efficacy and Safety of Sodium Oligomannate in the Prevention of PSCI (clinicaltrials.gov) - P=N/A | N=116 | Recruiting | Sponsor: Nanfang Hospital, Southern Medical University | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2023 ➔ Dec 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2025

Enrollment open • Trial completion date • Trial primary completion date • Cardiovascular • Cognitive Disorders • Ischemic stroke

Chinese Firm Halts Production of Controversial Alzheimer’s Drug (Bloomberg) - "A Chinese company that developed the country’s first indigenous therapy for Alzheimer’s disease has suspended production and sales of the drug, casting doubts on the treatment’s future. The drug’s license has expired and its renewal is now in the final stages of a regulatory review, during which it must stop commercial production and sales, Green Valley Pharmaceutical Co. said in an emailed statement to Bloomberg News on Tuesday....Green Valley’s drug - a seaweed-derived compound known as sodium oligomannate, or GV-971 - was hailed as a major advance when China’s drug regulator gave it conditional approval in 2019....Local and international medical experts have since questioned how effective it really is in slowing or reversing the cognitive declines of Alzheimer’s patients given the relatively short duration of - and the inconsistent results shown in - its late-stage clinical trial in China."

Commercial • Alzheimer's Disease

Screening and Intervention Study of Preclinical Alzheimer's Disease Cohort (ChiCTR) - P=N/A | N=2300 | Recruiting | Sponsor: The Affiliated GuangdongSecond Provincial GeneralHospital of Jinan University; The Affiliated GuangdongSecond Provincial GeneralHospital of Jinan Univ

New trial • Alzheimer's Disease • CNS Disorders

Sodium oligomannate disrupts the adherence of Ribhigh bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD Alzheimer's disease mouse (IMMUNOLOGY 2025) - "to gut epithelia via directly binding to Rib, which corrected the excess lactate, reduced SAA, and alleviated Th1-skewed inflammation. Together, we gained further insights between gut bacteria and AD progression and the mechanism of sodium oligomannate in treating AD.Keywords: Animals Rodent; Cells Th1/Th2 Cells; Infections Bacterial; Molecules Acute Phase Reactants; Tissues Mucosa"

Adherence • Preclinical • Alzheimer's Disease • CNS Disorders • Gastrointestinal Disorder • Infectious Disease • Inflammation

One evaluated mannute sodium capsule (GV-971) long-term Clinical studies of safety (ChiCTR) - P=N/A | N=2500 | Completed | Sponsor: Huashan Hospital, Fudan University; Huashan Hospital, Fudan University

New trial • Cognitive Disorders

SEX-SPECIFIC MODULATION OF AD-TYPE PATHOLOGY BY PERTURBATIONS OF THE GUT MICROBIOME (ADPD 2025) - "Our studies reveal that ABX- and GV-971-mediated attenuation of Aß and deposition and alterations in microglial biology occurs in a sex-specific manner and that in females, ovarian hormones play a central role in counteracting the beneficial effects of ABX- or GV-971 on neuropathology that are observed in males."

Amyloidosis • Inflammation

Polymers for the treatment of Alzheimer's disease. (PubMed, Front Pharmacol) - "Moreover, many polymers with inherent therapeutic properties have been developed, including the already marketed GV-971 as well as experimental polymers such as PLGA and CS oligosaccharide. This review summarizes the applications of polymers in AD treatment over the past few years and highlights their current limitations to help researchers better understand current advancements in polymer development and identify future research directions."

Journal • Review • Alzheimer's Disease • CNS Disorders • Oncology • Psychiatry

Multi-Targeting Phytochemicals for Alzheimer's Disease. (PubMed, Phytother Res) - "Food and Drug Administration in the United States has authorized various drugs for the effective treatment of AD, which include galantamine, rivastigmine, donepezil, memantine, sodium oligomannate, lecanemab, and aducanumab. It could be concluded that phytochemicals light serve as an effective therapy for AD. However, more mechanistic investigations are needed to determine the clinical implications of phytochemicals in AD treatment."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation

Comparison of the efficacy of updated drugs for the treatment on the improvement of cognitive function in patients with Alzheimer 's disease: A systematic review and network meta- analysis. (PubMed, Neuroscience) - "Donanemab and Lecanemab showed good efficacy in ADCS-ADL and CDR-SB, respectively. GV-971 is the best choice to improve ADAS cogs and NPI."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Sodium oligomannate disrupts the adherence of Ribhigh bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD transgenic mice. (PubMed, Cell Discov) - "to gut epithelia via direct binding to Rib, which corrected the excess lactate, reduced SAA, and alleviated Th1-skewed inflammation. Together, we gained further insights into the molecular link between gut bacteria and AD progression and the mechanism of GV-971 in treating AD."

Adherence • Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Gastrointestinal Disorder • Inflammation

Long-term Efficacy and Safety Study of GV-971 (clinicaltrials.gov) - P4 | N=800 | Active, not recruiting | Sponsor: Green Valley (Shanghai) Pharmaceuticals Co., Ltd. | Trial primary completion date: Jun 2024 ➔ Jan 2025

Trial primary completion date • Alzheimer's Disease • CNS Disorders

A Clinical Study to Evaluate the Long-Term Safety Sodium Oligomannate Capsules (GV-971) (clinicaltrials.gov) - P4 | N=2500 | Active, not recruiting | Sponsor: Green Valley (Shanghai) Pharmaceuticals Co., Ltd. | Trial primary completion date: Apr 2024 ➔ Jan 2025

Trial primary completion date • Alzheimer's Disease • CNS Disorders

Association Between the Gut Microbiota and Alzheimer's Disease: An Update on Signaling Pathways and Translational Therapeutics. (PubMed, Mol Neurobiol) - "Clinical studies using probiotics such as Bifidobacterium spp., yeast beta-glucan, and drugs such as sodium oligomannate and rifaximine have shown improvements in gut health, resulting in the amelioration of AD symptoms. This study incorporates the most current research on the pathophysiology of AD involving the gut microbiota and highlights the knowledge gaps that need to be filled to develop potent therapeutics against AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Metabolic Disorders • MYD88 • NLRP3 • STING • TLR4

Introduction of multi-dimension biomarkers application for a randomized, double-blind, singlesimulated clinical trial of sodium oligomannate on Alzheimer's disease (CTAD 2024) - No abstract available

Biomarker • Clinical • Late-breaking abstract • Alzheimer's Disease • CNS Disorders

Post-marketing Study of Sodium Oligomannate: Long-Term Safety and Effectiveness of an Agent Targeting the Gut Microbiome for the Treatment of Alzheimer's Disease (CTAD 2024) - No abstract available

Clinical • Late-breaking abstract • P4 data • Alzheimer's Disease • CNS Disorders

Introduction of multi-dimension biomarkers application for a randomized, double-blind, single-simulated clinical trial of sodium oligomannate on Alzheimer's disease (CTAD 2024) - No abstract available

Biomarker • Clinical • Alzheimer's Disease • CNS Disorders

Potential benefits of marine-derived compounds for slowing the advancement of Alzheimer's disease. (PubMed, J Asian Nat Prod Res) - "Marine-derived compounds from sponges, algae, and marine invertebrates can be used for neuroprotection, with fewer adverse effects than synthetic drugs. Various compounds such as bryostatin-1, docosahexaenoic acid, spirolides, and astaxanthin, GV-971, have demonstrated outstanding activity and bioavailability."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation

GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis. (PubMed, Nat Commun) - "A metabolomics analysis of cecal contents from GV-971-treated SAP mice further identifies short-chain fatty acids, including propionate and butyrate, as key metabolites in inhibiting macrophage M1 polarization and subsequent lethal inflammation by blocking the MAPK pathway. These findings suggest GV-971 as a promising therapeutic for SAP by targeting the microbiota metabolic immune axis."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • Pancreatitis • Transplantation

Approved drugs and natural products at clinical stages for treating Alzheimer's disease. (PubMed, Chin J Nat Med) - "However, recent breakthroughs in AD drug development, including the approvals of aducanumab, lecanemab, and sodium oligomannate (GV-971), have ended a nearly two-decade hiatus in the introduction of new AD drugs. Their distinct properties and mechanisms of action offer new avenues to complement and enhance existing AD treatment approaches. This review article aims to provide an overview of the recent advancements and prospects in AD therapeutics, focusing on both NPs and approved drugs."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia

GV-971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities. (PubMed, CNS Neurosci Ther) - "GV-971 attenuates the progression of NMOSD in murine models and reduces neuroinflammation and injury, likely through its effects on remodeling gut microbiota and peripheral inflammation and metabolic disorders."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Gastrointestinal Disorder • Immunology • Inflammation • Metabolic Disorders • Multiple Sclerosis • Neuromyelitis Optica Spectrum Disorder • Rare Diseases