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FDA Approves First Anti-diarrheal Drug for HIV/AIDS Patients
The FDA has approved Fulyzaq (crofelemer, Salix Pharmaceuticals) for the symptomatic relief of noninfectious diarrhea in adults with human immunodeficiency virus (HIV) infection and/or acquired immune deficiency syndrome (AIDS) who are receiving antiretroviral therapy (ART).
The FDA approval is based on results from a phase III, randomized, double-blind, placebo-controlled (1 month) and placebo-free (5 months) study of 374 HIV-positive patients with a history of diarrhea for 1 month or more who were being treated with ART. The primary efficacy endpoint was the proportion of patients experiencing one or two watery bowel movements per week during at least 2 of the 4 weeks of the placebo-controlled phase of the study. Patients who received concomitant anti-diarrheal medications or opiates were counted as clinical nonresponders.
A significantly larger proportion of patients taking Fulyzaq 125 mg twice daily experienced a clinical response compared with patients given placebo. In addition, statistically significant reductions from baseline to the end of the double-blind period also were observed for the number of watery bowel movements per day and for the daily stool consistency score among patients taking Fulyzaq compared with the placebo group. Further, the Fulyzaq treatment effect for clinical response (125 mg twice daily vs. placebo) was similar in subgroup analyses based on duration of diarrhea, the baseline number of daily watery bowel movements, the use of protease inhibitors, and the CD4 cell count. The most common adverse events in the study were respiratory-tract infection, bronchitis, cough, flatulence, and increased bilirubin levels.
Fulyzaq (crofelemer) is a first-in-class gastrointestinal (GI) agent derived from the Croton lechleri plant, which is native to northwestern South America. The drug demonstrates local antisecretory and antidiarrheal effects in the GI lumen and has minimal systemic absorption. At the recommended dosage of one 125-mg delayed-release tablet taken twice daily, Fulyzaq inhibits both the cyclic adenosine monophosphate (cAMP)-stimulated cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion (C1–) channel, and the calcium-activated C1– channel (CaCC).
The inhibition of CFTR and CaCC reduces the secretion of chloride ions, along with the water that enables their transport, out of the circulatory system and into the intestinal lumen. The secretion of chloride ions has been shown to cause diarrhea, with the associated symptoms of dehydration, electrolyte imbalance, abdominal cramping, urgency, and increased frequency.
Fulyzaq is expected to be available in early 2013.
Source: Salix Pharmaceuticals; January 2, 2013.