General Information

Mytesi (crofelemer) is extracted from the latex of the Croton lechleri tree. it reduces excess chloride ion secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) channel. The chloride channel CFTR regulates water balance in the intestines through control of chloride ion secretion and sodium absorption.

Mytesi is specifically indicated for symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on anti-retroviral therapy.

Mytesi is supplied as a delayed-release tablet for oral administration. The recommended dose is one 125 mg delayed-release tablet taken orally two times a day, with or without food. Tablets should not be crushed or chewed. Tablets should be swallowed whole.

Clinical Results

FDA Approval
The FDA approval of Mytesi was based on a randomized, double-blind, placebo-controlled (one month) and placebo-free (five month), multi center study. The study enrolled 374 HIV-positive patients on stable anti-retroviral therapy (ART) with a history of diarrhea for one month or more. The study had a two-stage adaptive design. In both stages, patients received placebo for 10 days (screening period) followed by randomization to crofelemer or placebo for 31 days of treatment (double-blind period). Only patients with 1 or more watery bowel movements per day on at least 5 of the last 7 days in the screening period were randomized to the double-blind period. Each stage enrolled patients separately; the dose for the second stage was selected based on an interim analysis of data from the first stage. In the first stage, subjects were randomized to one of three crofelemer dose regimens (125, 250, or 500 mg twice daily) or placebo. In the second stage, subjects were randomized to crofelemer 125 mg twice daily or placebo. Each study stage also had a five month period (placebo-free period) that followed the double blind period. Patients treated with crofelemer continued the same dose in the placebo-free period. In the first stage, patients that received placebo were re-randomized to one of the three crofelemer dose regimens (125, 250, or 500 mg twice daily) in the placebo-free period. In the second stage, patients that received placebo were treated with crofelemer 125 mg twice daily in the placebo-free period. The primary efficacy endpoint was the proportion of patients with a clinical response, defined as less than or equal to 2 watery bowel movements per week during at least 2 of the 4 weeks of the placebo-controlled phase. A significantly larger proportion of patients in the crofelemer 125 mg twice daily group experienced clinical response compared with patients in the placebo group (17.6% vs. 8.0%, 1-sided p < 0.01).

Mechanism of Action

Mytesi (crofelemer) is extracted from the latex of the Croton lechleri tree. It is an inhibitor of both the cyclic adenosine monophosphate (cAMP)-stimulated cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion (Cl-) channel, and the calcium-activated Clc hannels (CaCC) at the luminal membrane of enterocytes. The CFTR Cl channel and CaCC regulate Cl-and fluid secretion by intestinal epithelial cells. Crofelemer acts by blocking Cl secretion and accompanying high volume water loss in diarrhea, normalizing the flow of Cl and water in the GI tract.