Phase 2 Trial of Sodium Oligomannate in Parkinson Disease Greenlit by FDA

Shifu Xiao, MD, PhD

The FDA has accepted the investigational new drug (IND) application from Green Valley Pharmaceuticals’ and has allowed the company to go ahead with its phase 2 trial assessing sodium oligomannate (GV-971), an agent approved in China for Alzheimer disease (AD), in a global cohort of patients with early-stage Parkinson disease (PD).¹

This multicenter trial will include approximately 300 patients with early-stage PD who will be randomized to either sodium oligomannate or placebo for a 36-week period. Following that, patients may enter into a nonrandomized, 36-week, open-label extension for further testing. No information was provided as to when the study would begin.

Although the pathogenesis of PD is not entirely known, research has pointed to its associations with alpha-synuclein aggregation, neuroinflammation, oxidative stress, and mitochondrial dysfunction. It is currently the second most common neurodegenerative disease behind AD, which has also had research that has shown a link between gut inflammation and disease progression.

Sodium oligomannate is a seaweed-based oral compound derived from marine brown algae that is designed to promote a healthy gut microbiome. It specifically targets the gut-brain axis—the interplay between the nerve cells governing the intestines and those in the brain—and works to reduce inflammation by reconditioning the gut microbiota and inhibiting the abnormal balance of the byproducts of gut microbiota metabolism.

READ MORE: Roche Designing New Phase 2 Trial of Tominersen in Huntington Disease

After receiving fast track designation, China’s National Medical Products Administration approved sodium oligomannate for the treatment of mild-to-moderate AD and improving cognitive function on November 2, 2019. The drug is currently only approved in China, although several studies, including a notable phase 3 trial, have demonstrated its significant benefits.

Shifu Xiao, MD, PhD, et al conducted a phase 3, double-blind, placebo-controlled trial (NCT0229391) that included 818 participants with mild-to-moderate AD who were randomized to either 900 mg sodium oligomannate or placebo for 36 weeks. At the conclusion of the study, a significant drug-placebo difference in the Alzheimer’s Disease Assessment Scale (ADAS-Cog 12) favoring the study drug was present at each measurement time point, measurable at week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was –2.15 points (95% CI, –3.07 to –1.23; P <.0001; effect size, 0.531).²

There were no statistically significant treatment effects for prespecified secondary outcomes, which the authors noted that they were underpowered to show as the sample size was calculated based on the primary end point. Notably, the trial did not require a diagnostic amyloid biomarker at screening, thus likely including participants who had dementia that was not due to AD; however, approximately 50% of the participants were apolipoprotein e4 carriers with higher likelihood of amyloid deposition.

In April 2020, the FDA accepted an IND application for a phase 3 study of GV-971 in an expected cohort of more than 2000 patients with mild-to-moderate AD. Green Valley is working with IQVIA, the world’s largest research organization for clinical trial operation, to manage the study, which comprises of a 12-month double-blind treatment period and a 6-month open-label period. The company is planning to complete the trial in 2024, with a new drug application submission expected to follow by 2025.³

REFERENCES

1. Green Valley obtains IND approval from US FDA for sodium oligomannate’s global phase 2 clinical trial in treating Parkinson disease. News release. Green Valley Pharmaceuticals. January 17, 2022. Accessed January 24, 2022. https://www.prnewswire.com/news-releases/green-valley-obtains-ind-approval-from-us-fda-for-sodium-oligomannates-global-phase-ii-clinical-trial-in-treating-parkinsons-disease-301461838.html

2. Xiao S, Chan P, Wang T, et al. A 36-week multicenter, randomized, double-bllind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer dementia. Alzheimers Res Ther. 2021;13(1):62. doi:10.1186/s13195-021-00795-7

3. Green Valley obtains IND approval from US FDA for sodium oligomannates international, phase 3 clinical study. News release. Green Valley Pharmaceuticals. April 27, 2020. Accessed January 24, 2022. https://www.biospace.com/article/releases/green-valley-obtains-ind-approval-from-u-s-fda-for-sodium-oligomannate-s-international-phase-iii-clinical-study/