FDA Delays Decision on Diarrhea Drug for HIV/AIDS Patients
Active ingredient in crofelemer needs further review (Sept. 5)
Salix Pharmaceuticals, Ltd., based in Raleigh, N.C., announced on September 5 that the FDA is still reviewing the company’s New Drug Application (NDA) for crofelemer 125-mg tablets, for the proposed indication of symptomatic relief of noninfectious diarrhea in patients with human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS) on antiretroviral therapy. The FDA informed the company that it will not take final action by the scheduled Prescription Drug User Fee Act (PDUFA) goal date of September 5, 2012.
The primary sticking point is the production and control of the active pharmaceutical ingredient in crofelemer — a complex mixture that is the first botanical product to be reviewed by the FDA for oral use. Further discussion is needed to ensure compliance with the manufacturing and product quality requirements of the Food, Drug, and Cosmetic Act.
Salix anticipates an action by the FDA on the company’s NDA by the end of the first quarter of 2013.
Salix describes crofelemer as an antidiarrheal botanical drug substance. Crofelemer has minimal absorption and no effect on gut motility. The drug’s mechanism of action is through inhibition of both the cystic fibrosis transmembrane conductance regulator (CFTR) protein chloride-ion channel and the calcium-activated chloride-ion channel (CaCC). Crofelemer acts by blocking chloride ion-channel secretion and accompanying high-volume water loss in diarrhea, thereby normalizing the flow of chloride ions and water in the gastrointestinal tract.
Diarrhea remains a common problem for patients with HIV/AIDS that often negatively impacts their quality of life. Diarrhea can cause these patients to discontinue or prematurely switch antiretroviral therapy (ART) regimens.
Approximately 1.2 million people in the U.S. have HIV/AIDS, and about 40% of those patients experience either episodic or chronic diarrhea. This condition not only significantly reduces quality of life, but also results in weight loss, depression, and reduced social interaction, and often increases direct and indirect healthcare costs.
For more information, visit the Salix Pharmaceuticals Web site.