RDX5791 potently and selectively inhibits NHE3, a sodium transporter on the surface intestinal epithelia. RDX5791 has completed phase I clinical studies where the safety of the compound was demonstrated in healthy adult volunteers. Inhibition of sodium absorption from the GI tract was evidenced by a decrease in urinary sodium and an increase in fecal sodium. It was shown in Ardelyx’s phase I trial that RDX5791, in a dose-dependent manner, can cause a loosening of the stools and decreased time-to-first-stool similar to that seen in healthy adults with other approved IBS-C and constipation drugs. Based on these data, and preclinical models of IBS-C, it is believed that RDX5791 may reduce abdominal pain, discomfort and bloating, making it potentially an ideal candidate for use in patients with IBS-C and chronic constipation. RDX5791 is currently being evaluated in a 180-patient phase IIa clinical study for the treatment of IBS-C. We expect this data to be available by early 2012. Based on promising pre-clinical data, RDX5791 may also be evaluated for its potential use in opioid bowel dysfunction.
NHE3 inhibition for the treatment of hypertension
Based on multiple pre-clinical models and the initial RDX5791 phase study, we believe that intestinal sodium blockade may be an ideal approach for treating hypertension by blocking the absorption of 2 -3.5 grams of dietary salt, resulting in a reduction of blood pressure.
While we do not yet know the safety or efficacy of RDX5791 in patients with hypertension, studies have demonstrated significant benefits in morbidity, mortality, and public health expenditures when dietary salt intake is lowered by a magnitude equivalent to the amount of sodium RDX5791 has been demonstrated to block in early studies.
For example, RDX5791 tested in a well-established CKD model of hypertension, significantly reduced blood pressure and proteinuria, as well as heart hypertrophy and kidney hyperplasia. Based on these and other results, Ardelyx believes that RDX5791 (and RDX008 as a next generation NHE3 inhibitor) will be beneficial in treating hypertension.
Ardelyx is currently evaluating RDX5791 in a Phase Ib study to optimize the amount of sodium that can be diverted. Results from this study, expected in early 2012, are expected to define the dosing and biological effects of RDX5791 in preparation for its evaluation in hypertensive patients.
