WHIPPANY, N.J.—Bayer wrapped up the first quarter with encouraging news, having announced that the CHICO (CHagas disease In Children treated with NifurtimOx) part of its Phase 3 study of nifurtimox met its primary endpoint. The study evaluated the safety, efficacy and pharmacokinetics of nifurtimox in 330 pediatric patients with acute or chronic Chagas disease, and was conducted at 25 investigational sites in Argentina, Bolivia and Colombia between 2016 and 2018.
CHICO's primary endpoint was serological response at one year after the end of treatment, and 60-day nifurtimox treatment was found to be superior to the historical placebo control. The clinical study was the largest to date of patients with Chagas disease.
“Children are the most vulnerable patient group suffering from Chagas disease. With the successful completion of the CHICO study, an important milestone in our long-standing commitment to improve the treatment of Chagas has been achieved,” said Dr. Joerg Moeller, member of the executive committee of Bayer AG´s Pharmaceutical Division and head of research and development.
Chagas is an infectious disease that is caused by the Trypanosoma cruzi parasite and is transmitted to humans by the feces of “kissing bugs,” or triatomines. It is sometimes known as a silent or “forgotten disease” due to being mostly asymptomatic for years, and even during the acute phase immediately after infection, most patients are unaware they’re infected and only one-third of those infected present with non-specific symptoms such as fever, fatigue and swollen lymph glands for weeks. Without treatment, Chagas disease moves into a chronic lifelong phase. While this is asymptomatic for most patients, roughly 30 percent develop chronic, irreversible complications such as cardiomyopathy or other heart conditions, abnormal enlargement of the digestive tract, or even neurological or mixed conditions.
This disease, like others, can be transmitted during pregnancy or birth from mother to child, and can also be transmitted via blood transfusions or organ transplantations. The World Health Organization estimates that some 8 million people are infected with this disease globally, with Latin America as a key area of high infection. Despite these numbers, less than 1 percent of those infected get treatment, which is attributed both to low disease awareness and limited access to treatment.
At present, Chagas disease is treated with two nitroheterocyclic compounds: nifurtimox and benznidazole. While nifurtimox isn’t approved by the FDA, it is being made available in a 120 mg tablet form exclusively through the U.S Centers for Disease Control and Prevention under an investigational protocol. In the CHICO trial, Bayer used a newly developed formulation of the drug that can be dissolved in water for easier administration to young patients.
“An adequate dispersable formulation of nifurtimox is a big step forward toward achieving the goal of treating all infected children,” commented Dr. Jaime Altcheh, head of the Department of Parasitology and Chagas disease at the Ricardo Gutierrez Children’s Hospital in Buenos Aires, Argentina, and coordinating investigator of the trial. "Early treatment after infection is very important to prevent manifestation of the disease in adulthood."
In other recent and encouraging news for those dealing with Chagas disease, the Drugs for Neglected Disease initiative (DNDi) found that a two-week course of treatment for adults with chronic Chagas disease showed similar efficacy and fewer side effects than the standard twice-daily, eight-week treatment regimen. A Phase 2 trial—the BENDITA study (Benznidazole New Doses Improved Treatment & Associations)—evaluated benznidazole as a monotherapy and in combination with fosravuconazole, an antifungal agent developed by Eisai Co. Ltd. On the shorter treatment course, patients saw similar results as those who received the eight-week course, with no sign of the parasite in their blood at six and 12 months after completing treatment.
DNDi conducted the trial in collaboration with CEADES (Fundacion Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio Ambiente), ISGlobal, Eisai, Argentinian pharmaceutical company manufacturer of benznidazole Elea and associated non-profit foundation Fundación Mundo Sano, among others, and it was funded by the Global Health Innovative Technology Fund (GHIT).
More growth and developments are likely on the way for this disease, as well. A report by Coherent Market Insights titled “Chagas Disease Treatment Market–Global Industry Insights, and Forecast till 2025” noted that increased migration from countries where Chagas is endemic is expected to drive growth for the treatment market. Increased R&D in the market and recent and upcoming drug approvals are also expected to boost growth. Coherent Market Insights reports that the Chagas disease treatment market was estimated at $5.67 million in 2016 and is expected to grow at a compound annual growth rate of 7.3 percent from 2017 to 2025. The report also noted that in 2017, benznidazole held approximately 88.63 percent of the market, with nifuritmox holding the remainder.