Merck announced plans to initiate a phase II investigational proof-of-concept clinical study to evaluate its oral antifungal agent posaconazole for the treatment of chronic Chagas disease. Chagas disease results from infection with the parasite Trypanosoma cruzi that is spread by biting insects. The disease is estimated to affect approximately eight million people in Latin America, of whom approximately 30-40 per cent will develop serious cardiac disease, digestive disease, or both as a result of this infection. Recognized by the World Health Organization (WHO) as a neglected tropical disease, Chagas disease also is becoming an emerging health problem in non-endemic areas through migration of infected populations from endemic areas. Currently, only two drugs are approved for treatment: benznidazole and nifurtimox.
"While significant progress has been made in recent years in the prevention of the transmission of this potentially life-threatening disease, no new drugs have been approved for the treatment of chronic Chagas disease in over three decades," said Roger J. Pomerantz, M.D., F.A.C.P., global franchise head for infectious diseases and senior vice president, Merck Research Laboratories.
In planning the study to evaluate posaconazole, Merck has consulted with international agencies and research organizations to identify the current medical needs and reach consensus on a study design for posaconazole in asymptomatic chronic Chagas disease. The proposed study is a randomized, placebo-controlled phase II study of posaconazole oral suspension (400 mg twice daily) given for 60 days, either as monotherapy or concomitantly with benznidazole. Benznidazole monotherapy will serve as an active control.
The study is planned to enrol 160 adult patients with chronic Chagas disease at several sites in South America and follow them for a total of 360 days. The study will utilize polymerase chain reaction (PCR) to evaluate the levels of Trypanosoma cruzi in blood samples as the primary endpoint for response to treatment. Safety will be monitored by an external independent Data and Safety Monitoring Board (DSMB) on an ongoing basis and the DSMB will make recommendations as appropriate. Results from the study are expected in 2012. If successful, phase III clinical studies with posaconazole would follow. Merck looks forward to working with interested partners to facilitate access if posaconazole is shown to be beneficial in the treatment of chronic Chagas disease.
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and was discovered in 1909 by the Brazilian physician Carlos Chagas (1879-1934). It continues to represent a serious social and economic problem in many Latin American countries, with approximately 20,000 deaths each year attributed to Chagas disease. Chagas disease is transmitted to humans mainly by insect bites, but also can be transmitted via blood transfusion, transplantation and vertically from mother to infant. Rarely, it can be contracted by ingestion of contaminated food or liquid. The initial phase of acute infection lasts for four-to-eight weeks and the chronic phase persists for the person's lifespan. In most individuals, irrespective of the mode of transmission, acute Chagas infection is usually asymptomatic. The clinical outcome of the chronic phase of Chagas disease ranges from the absence of signs and symptoms of disease to severe illness and premature death. Typical clinical manifestations of the chronic phase are related to the pathological involvement of the heart, esophagus, colon, or a combination, and are grouped into three major forms: cardiac, digestive, and cardiodigestive. It may take more than 20 years from the time of the original infection to develop serious heart or digestive disease. Benznidazole and nifurtimox are the only drugs with proven efficacy against Chagas disease. Benznidazole is usually used for first-line treatment.
Merck has a long history of engaging in public-private partnerships and research initiatives to develop and foster access to its medicines and vaccines worldwide.
Posaconazole is approved and marketed in the United States, European Union and several other countries as Noxafil (posaconazole) oral suspension. In the US, Noxafil is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients, 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised, such as haematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with haematologic malignancies with prolonged neutropenia from chemotherapy. Noxafil also is indicated for the treatment of oropharyngeal candidiasis (OPC), including OPC refractory to itraconazole and/or fluconazole.