FDA grants priority review to GI agent for controlling diarrhea in HIV/AIDS patients

February 7, 2012

FDA has granted priority review to crofelemer 125-mg tablets (Salix Pharmaceuticals) for the control and symptomatic relief of diarrhea in patients with HIV/AIDS on anti-retroviral therapy (ART).

FDA has granted priority review to crofelemer 125-mg tablets (Salix Pharmaceuticals) for the control and symptomatic relief of diarrhea in patients with HIV/AIDS on anti-retroviral therapy (ART).

According to Salix, crofelemer is a first-in-class, gastrointestinal agent of botanical origin. This gut-targeted, orally administered, anti-secretory, anti-diarrheal agent that has minimal absorption. The locally acting product also is believed to possess dual novel mechanisms of action that might be effective in treating both acute infectious diarrhea and chronic diarrhea, the company said in a press release.

Approximately 50% of the 1 million people in the United States living with HIV/AIDS are currently taking an ART, and approximately 30% of HIV/AIDS patients on ART (approximately 150,000 patients) experience episodic or chronic diarrhea. Diarrhea in this patient population can result in weight loss, reduced quality of life, poor compliance with ART, and increased healthcare costs.

Studies support the use of crofelemer, the company reported, as an anti-secretory anti-diarrheal agent that may provide relief to patients through the inhibition of chloride secretion by both gut Cystic Fibrosis Transmembrane Conductance Regulator Protein (CFTR) as well as gut calcium-activated chloride channel (CaCC).

Inhibiting CFTR and CaCC prevents the secretion of chloride and other ions, along with the water that passively follows chloride, out of the body into the intestinal lumen. This secretion leads to diarrhea, with the associated symptoms of dehydration, electrolyte imbalance, abdominal cramping, urgency, and increased frequency.

Additionally, crofelemer, unlike other anti-diarrheal agents, does not affect gut motility. In trials to date, crofelemer is well tolerated, and demonstrates a safety profile comparable to placebo. Crofelemer, if approved, would be a first-in-class CFTR inhibitor as well as a first-in-class CaCC inhibitor that would work as an anti-secretory anti-diarrheal drug, according to Salix.

“We are pleased with the FDA’s acceptance of the NDA for crofelemer and their decision to grant Priority Review for our application,” Bill Forbes, PharmD, executive vice president, Medical, Research and Development, and chief development officer, Salix, said in a company press release. “This review classification signals that the FDA believes that crofelemer has the potential to provide a significant advance in the treatment of HIV/AIDS-associated diarrhea for patients on ART. We believe the availability of crofelemer has the potential to change the treatment paradigm for HIV/AIDS patients suffering from diarrhea.”