Benznidazole
Chagas disease is a parasitic infection caused by a protozoan organism called Trypanosoma cruzi affecting millions of people, primarily in rural areas of Mexico, Central and South America. In the US, Centers for Disease Control and Prevention (CDC) estimates there are approximately 300,000 infected people. An increasing number of cases have also been reported in Canada, Europe, Japan and Australia.
The World Health Organization (WHO) and the CDC have designated Chagas disease as a neglected tropical disease. The FDA also added Chagas disease to its list of neglected tropical diseases in 2015 and has called it an “emerging public health concern.” Unlike in Latin America where vector transmission through triatomine insects (often called ‘kissing bugs’) is the primary mode of infection, it is thought that the main cause of infection in the US is by congenital transmission from mother to fetus. Other sources of infection, particularly in endemic countries, are blood transfusions, organ transplants and, on rare occasions, oral ingestion.
The disease has an acute and chronic stage. The acute stage is not associated with symptoms in 95% of cases. Symptoms that do appear can include fever or swelling around the site where the parasite entered the body. While the acute stage does not often cause significant morbidity, children and immunosuppressed individuals have a higher risk of mortality. The disease enters into the chronic stage post-infection, which can be a few weeks or longer after the acute stage. Many infected people remain asymptomatic for life. However, chronic infection can lead to serious complications and potentially death in an estimated 20-30% of infected individuals, usually 10-30 years after the initial infection. Complications include cardiovascular, gastrointestinal and neurological diseases. According to the CDC, treatment is recommended for those with acute infection, those with congenital infections and children with chronic infection. It also states that adults with chronic infection may benefit from being treated.
Benznidazole, a nitroimidazole derivative, is one of two drugs (nifurtimox is the other) that have shown efficacy and safety for treatment of Chagas disease for over 40 years. The anti-parasitic activity of benznidazole is believed to be secondary to the production of reactive metabolites in the parasite that leads to alkylation and oxidative damage of vital elements such as DNA and RNA in the parasite. Benznidazole is the first line treatment, where it is approved, for Chagas disease because of its efficacy and safety profile, particularly in pediatric patients. Currently the worldwide drug supply is unstable due to manufacturing issues. Moreover, neither benznidazole or nifurtimox has been approved in the US. The only way for patients with Chagas disease in the US to access treatment is through an investigational protocol administered by the CDC.
KaloBios, in collaboration with Savant Neglected Diseases LLC, is developing a version of benznidazole with the intent of securing FDA approval in the US and to potentially make this version of benznidazole available globally.