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 appears to be 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 weight loss in a subset of patients. Complete clinical data remain confidential and will be presented at a major diabetes conference in due course.
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.
Diabetes Discovery Programs
Novel Insulin Sensitizing Target
Verva preclinical studies have determined that the mechanism by which VVP808 exerts its effect on blood glucose levels is different to its mode-of-action in glaucoma. Verva has a dedicated program to identify the biological target(s) through which VVP808 exerts its insulin sensitizing effects. Success in the VVP808-002 clinical trial will partially validate the relevance of this target in diabetes and its utility in diabetes drug development.
Verva is utilizing mechanistic and structural knowledge derived from studies with VVP808 and the target identification program to develop proprietary next-generation insulin sensitizers with improved efficacy and safety relative to current therapies. Preliminary in silico and in vitro studies identified 5 potential new development scaffolds and Verva has an on-going medicinal chemistry program to identify proprietary NCEs as potential insulin sensitizers.
Verva’s diabetes assets and technologies are the result of a decade of research acknowledging that type 2 diabetes is a multifactorial disease with different causes and diverse patient etiologies. Central to the diabetes effort is the Gene Expression Signature (GES) technology, which measures changes in expression of a critical selection of genes that are modulated when diabetic cells are rendered “normal” by treatment with anti-diabetic medications. Medium-to-longer term value-generation for Verva will be achieved by application of different GES types to identify medications that are optimised to groups of diabetic patients with different underlying diabetes pathologies. This “genomics-driven, personalised medicine” may lead to safer, more effective diabetes therapies.