Cryptococcal meningitis is a life-threatening fungal infection of the brain and spinal cord. The infection occurs most often in immunocompromised patients such as HIV patients, transplant recipients, and oncology patients. An estimated 3,400 hospitalizations related to cryptococcal meningitis occur annually in the United States. The primary pathogen causing cryptococcal meningitis is Cryptococcus neoformans. Cryptococcal meningitis is characterized by flu-like symptoms that rapidly progress to include CNS symptoms such as high fever, neck stiffness, mental status changes and seizures. The disease is almost always fatal without treatment. Standard therapy in developed countries consists of intravenous administration of amphotericin B and oral flucytosine, typically for two weeks. Following acute therapy, patients are usually treated with oral fluconazole for 6 - 12 months in order to prevent relapse. Despite access to advanced medical care and the availability of current antifungal agents, the three-month mortality rate of cryptococcal meningitis can range up to 21% in medically developed countries.
While relatively uncommon in the United States and Europe, cryptococcal meningitis is a very common disease in the developing world due to the high incidence of HIV infection and AIDS. Approximately one million cases of cryptococcal meningitis occur in the developing world each year, resulting in a mortality rate of approximately 55-70% within three months of infection. In regions where intravenous amphotericin B and oral flucytosine are not commonly available, fluconazole is the most widely used agent since it is administered orally and is more widely available. However, fluconazole monotherapy is mostly ineffective. According to the Centers for Disease Control and Prevention, the greatest burden of cryptococcal meningitis occurs in sub-Saharan Africa, where mortality due to the disease is estimated to be as high as 70%.
VT-1129 is currently in a Phase 1 single-ascending dose study in healthy volunteers. Upon successful completion of Phase 1 testing, VT-1129 will be tested in a Phase 2 trial for the oral treatment of cryptococcal meningitis.