VVP808-002 Clinical Study
Verva’s clinical candidate, VVP808, is a non-thiazolidinedione insulin sensitizer for use in the treatment of type 2 diabetes mellitus (T2DM). The active ingredient of VVP808 (methazolamide) was originally approved in North America over 50 years ago as a treatment for glaucoma. Its unexpected anti-diabetic activity was identified using Verva’s proprietary Gene Expression Signature (GES) discovery platform. VVP808 has a mode-of-action that is different to existing diabetes medicines, providing an important new line of treatment for T2DM.
In June , 2012, Verva announced the top-line results of a Phase 2 clinical proof-of-concept study evaluating VVP808 in patients with T2DM. The clinical study achieved its protocol-specified primary efficacy endpoint, a reduction in the diabetes marker HbA1c compared to placebo after 24 weeks of treatment. The drug was safe and well-tolerated and the study identified potential additional clinical benefits of VVP808 beyond HbA1c reduction, including improvements in markers of liver function and weight loss in metformin co-treated patients.
The VVP808-002 clinical trial was a randomized, placebo-controlled, double-blinded study evaluating the safety and efficacy of VVP808 in T2DM patients who were (i) not taking any other glucose modulating medications; or (ii) currently stable on metformin alone. Participants received oral VVP808 or placebo daily for 24 weeks. The primary efficacy endpoint of the study was a reduction in HbA1c levels in participants receiving VVP808 compared to those receiving placebo. Secondary endpoints included fasting blood glucose; HOMA-IR index; and improvement in participant risk factors such as body weight, waist circumference, blood pressure and lipid profile.
Verva Discovery Programs
Novel Therapeutic Target
Verva preclinical studies have determined that the mechanism by which VVP808 exerts its effect in diabetes is different to its known mode-of-action in glaucoma. Moreover, the proposed VVP808 novel therapeutic target has not previously been evaluated in diabetes therapy. Verva is pursuing characterization of the VVP808 mode-of-action in diabetes and exciting recent results suggest that molecules acting at the VVP808 novel therapeutic target may have additional application in significant unmet medical needs beyond metabolic disorders. Success in the VVP808-002 clinical trial partially validates the relevance of this target in diabetes and its utility in diabetes drug development.
VVP100X: Next Generation Molecules from VVP808
Verva is utilizing mechanistic and structural knowledge derived from studies with VVP808 and the target identification program to develop proprietary, next-generation medicines optimized to the VVP808 novel therapeutic target. Preliminary in silico and in vitro studies identified multiple development scaffolds and Verva has generated a library of molecules for target screening.