An investigational new drug developed by PATH’s Drug Development program to treat acute secretory diarrhea is entering the next phase of clinical development following the successful completion of clinical studies in the United States.
iOWH032, designed to treat diarrhea caused by diseases such as cholera, has been previously investigated in animal diarrhea studies, preclinical toxicology studies, and first-in-human trials in healthy American volunteers. Those studies found that it was generally safe and well tolerated.
The next study, a phase 2(a) trial conducted in partnership with the International Centre for Diarrhoeal Disease Research, Bangladesh, will assess the pharmacokinetics, safety, and tolerability of iOWH032 in Bangladeshi healthy volunteers and in patients with acute cholera. Findings will support dose selection for a subsequent proof-of-concept trial to assess the safety and efficacy of iOWH032 in treating cholera in a large number of patients.
Unlike most currently available medications, iOWH032 works to treat diarrheal processes directly by reducing fluid secretion, shortening both the duration and severity of symptoms. If approved, the drug would be used in conjunction with oral rehydration and other proven therapies and could encourage wider adoption of and compliance with those treatments by quickly reducing diarrheal symptoms.
iOWH032, a synthetic small molecule with novel biological activity, is designed to prevent dehydration and provide rapid relief of diarrheal symptoms before they become fatal. The drug candidate works by inhibiting the cystic fibrosis transmembrane conductance regulator (CFTR), which is the primary driver of secretion in cases of diarrhea caused by enterotoxigenic or cholera bacteria. iOWH032 acts as a CFTR inhibitor by blocking the flow of chloride ions and thus the loss of water out of the gastrointestinal tract.
The development of iOWH032 is funded by the Bill & Melinda Gates Foundation and has been led by OneWorld Health, which affiliated with PATH in 2011 to establish our Drug Development program.