Phase 2 Clinical Trial for VG081821AC in Parkinson's Disease Enrolls Completed

Vimgreen Pharmaceuticals, a research-driven company based in Hangzhou, China, has announced the completion of participant enrollment for its Phase 2 clinical trial evaluating VG081821AC. This novel pharmaceutical compound, which acts as both an adenosine A2A receptor (A2AR) antagonist and an inverse A2AR agonist, is being tested as a treatment for early-to-mid stage Parkinson's disease (PD). The clinical trial has successfully enrolled 150 participants who have been randomly assigned to one of three groups: a high-dose VG081821 group, a low-dose VG081821 group, and a placebo group, each with an equal number of participants.

The trial spans 12 weeks and is designed as a multicenter, randomized, placebo-controlled, double-blind study. The primary objective is to assess the safety and effectiveness of VG081821 as a standalone treatment for early-to-mid stage PD patients. The primary endpoint focuses on the change in motor symptoms, measured by the movement disorder society-unified Parkinson's disease rating scale (MDS-UPDRS) part III score, from the baseline over the 12-week treatment period.

Current therapies for PD primarily rely on strategies that replace dopamine, such as L-Dopa, dopamine agonists, MAO-B inhibitors, and COMT inhibitors. These treatments aim to boost dopamine levels or mimic its function. While L-Dopa is particularly effective in managing PD motor symptoms, it often leads to motor complications like wearing-off, ON–OFF phenomena, and dyskinesia over long-term use. Additionally, existing PD treatments are mainly symptomatic and do not slow disease progression.

VG081821, as an A2AR antagonist functioning through non-dopaminergic pathways, holds the potential to mitigate or delay motor complications if administered early in the disease course. Unlike traditional A2AR antagonists, VG081821 also acts as an inverse agonist, which might provide additional therapeutic benefits and greater efficacy in addressing motor dysfunction in PD. This dual action could offer both symptomatic relief and disease-modifying advantages, presenting an improved treatment option for PD patients.

In prior trials, A2A antagonists were typically used as adjunct treatments combined with L-Dopa to alleviate "off" episodes in advanced PD patients, leading to the approval of Istradefylline in the US and Japan. However, according to Sanxing Sun, President and CEO of Vimgreen, VG081821 is intended for use as monotherapy to enhance motor function in the early to mid stages of PD. As the disease progresses, it can be supplemented with low doses of L-Dopa, potentially reducing L-Dopa-related issues and extending the quality of life for PD patients.

A noteworthy aspect of the current Phase 2 trial involves analyzing A2AR gene expression levels in human peripheral blood mononuclear cells (PBMCs) of PD patients, as elevated A2AR gene expression in PBMCs is noted among this patient group. This analysis may reveal a correlation between drug efficacy and A2AR expression, potentially positioning VG081821 as a precision medicine. The trial is expected to conclude in November.

VG081821AC, developed by Vimgreen Pharmaceuticals, is a potent and selective antagonist of the adenosine A2A receptor, which is heavily distributed in the basal ganglia and striatum, regions involved in motor function regulation. This makes A2AR an appealing non-dopaminergic target for PD treatment.

Vimgreen Pharmaceuticals, based in Hangzhou, focuses on modulating adenosine signaling due to its crucial role in various physiological processes, including nervous system regulation, immune response, and vascular function. The company has made significant strides in understanding adenosine signaling in disease progression, creating therapeutic opportunities for treating various conditions. In addition to VG081821 for PD, Vimgreen is also developing VG290131, an A3 agonist for treating non-alcoholic steatohepatitis (NASH).