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Therapeutics for Rare and Neglected Diseases

Development of the Novel Antifungal VT-1129 for Cryptococcal Meningitis

Cryptococcal meningitis (CM) results from fungal infections that are particularly prevalent in immune-compromised patients. CM is the second leading cause of HIV-related deaths in sub-Saharan Africa, with estimates of 500,000 deaths per year. Current therapies are only marginally effective. The purpose of this project is to develop a novel therapeutic that would greatly improve treatment of CM.

SCIENTIFIC SYNOPSIS

CM results from infection by the encapsulated yeasts Cryptococcus neoformans and Cryptococcus gattii and is observed almost exclusively in immune-compromised individuals. The enormous population of HIV-infected people in sub-Saharan Africa (estimated to be more than 20 million), with inadequate access to antiretroviral therapy, is highly susceptible to this disease. The most common drug treatment for CM in this patient population is high-dose fluconazole monotherapy, but it achieves only a 40 percent survival rate after 10 weeks of treatment. A more potent anti-fungal drug that can be given orally once a day would likely provide a significant improvement in survival for this neglected population. This project includes pre-clinical Investigational New Drug (IND)–enabling studies that will evaluate VT-1129 as a novel, oral, stand-alone drug candidate for the treatment of CM.

LEAD COLLABORATOR

Viamet Pharmaceuticals, Inc. , Morrisville, N.C .
Edward Garvey

PUBLIC HEALTH IMPACT

The global incidence of CM and the mortality rate due to CM infection are increasing. Current drugs (FLC, amphotericin and flucytosine) are  marginally effective at best. This project aims to develop novel therapeutics that have the potential to save more than 100,000 lives annually. These new therapies also have the potential to be the first effective therapy for the treatment of C. gattii, an emerging and aggressive fungus that infects non-immunocompromised individuals in industrialized geographies.

OUTCOMES

TRND researchers conducted validation studies for the lead compound, VT-1129, including pharmacokinetic, efficacy, and toxicology studies in rodents and non-rodents, enabling selection of an optimal dosing regimen to balance efficacy and safety. The TRND team optimized a synthetic process for scaled-up production of drug at a low cost that will support treatment of patients in the developing world. Additional collaborative studies were completed with the Centers for Disease Control and Prevention (CDC) to test the in vitro efficacy of the molecule against 400 fungal strains from Africa. This TRND support enabled Viamet to successfully raise venture capital funding to continue development of the de-risked candidate and receive Qualified Infectious Disease Product and Fast Track designations from the Food and Drug Administration (FDA). The purpose of these FDA designations is to get important new drugs to patients more quickly by facilitating development and expediting review. Viamet successfully filed an Investigational New Drug (IND) application with the FDA to initiate clinical trials.

RELATED INFORMATION

News Release: Viamet Receives Fast Track Designation from the FDA for VT-1129 for the Treatment of Cryptococcal Meningitis (PDF - 52KB) (June 2016)

News Release: FDA Grants QIDP Designation to VT-1129 for Treatment of Cryptococcal Meningitis (PDF - 60KB) (September 2015)

Last updated: 05-11-2017
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