We are developing A3384 for bile acid malabsorption disease (BAM). A3384 is a proprietary formulation designed to deliver a drug known as cholestyramine directly to the colon. Cholestyramine is a bile acid sequestrant that acts by binding to bile acids in the GI tract to create insoluble complexes that are more easily secreted. These complexes replace bile acids that would otherwise stimulate electrolyte and water secretion in the small bowel and lead to diarrhea.
Although cholestyramine is approved in the United States (as well as Japan and many countries in Europe) as an adjunctive therapy to diet for the reduction of elevated serum cholesterol in certain patients and for the relief of pruritus associated with partial biliary obstruction, we believe that it is commonly prescribed off label to treat BAM. However, cholestyramine is typically taken as a powder that does not dissolve in water and has been described as “drinking sand.” As a result, many patients cannot tolerate cholestyramine and its benefit in the treatment of BAM has been limited. We believe that a formulation that has a more favorable tolerability profile than conventional bile acid sequestrants can benefit patients with BAM.
We have completed a Phase 2 clinical trial of a prototype of A3384 in 19 subjects with BAM. In the study, we saw encouraging signals of efficacy on some endpoints, including change in number of bowel movements and daily episodes of diarrhea, and the A3384 prototype was generally well tolerated. Based on the findings in the study, we embarked on an extensive pharmaceutical development program designed to identify an optimized formulation of A3384 and are in the final stages. In our next clinical trial in BAM, we plan to evaluate up to two distinct tablet formulations of A3384 designed to deliver cholestyramine directly to the colon.