Contacts: Kurtis Pivert • (202) 699-0238 • [email protected]Bob Henkel • (202) 557-8360 • [email protected]

PILOT STUDIES FIND NEW DRUG COULD HELP REDUCE DIETARY PHOSPHORUS ABSORPTION

Preliminary studies of small-molecule inhibitor of NHE3 show potential for reducing phosphorus in patients with kidney disease

Highlight• Researchers presented two preliminary studies at ASN Kidney Week 2014 in Philadelphia, PA, that demonstrate the potential of a small-molecule inhibitor of NHE3 to help reduce phosphorus absorption in patients with kidney disease. • Patients with reduced kidney function are unable to maintain normal levels of phosphorus, which can lead to hyperphosphatemia.

More than 20 million Americans have kidney disease

Newswise — Philadelphia, PA (December 2, 2014) — Researchers presented two preliminary studies at ASN Kidney Week 2014 in Philadelphia, PA, that demonstrate the potential of tenapanor—a minimally-systemic inhibitor of the intestinal sodium/proton exchanger subtype 3 (NHE3)—to help reduce phosphorus absorption in patients with kidney disease. Patients with chronic kidney disease (CKD) have impaired kidney function and are unable to excrete enough phosphorus to maintain normal levels of phosphorus, which can lead to such adverse effects as hyperparathyroidism and bone and cardiovascular diseases.

Previous studies have shown that tenapanor can reduce the absorption of sodium. In the first study presented at ASN Kidney Week 2014, researchers used two animal models to determine if tenapanor could also reduce phosphorus absorption.

Investigators found that tenapanor reduced phosphorous absorption in the rodent model demonstrated by an increase in fecal phosphorus excretion in animals receiving the drug compared to controls. A second model examining cardiovascular effects found reductions in vascular calcification markers for animals receiving tenapanor. “These results suggest that tenapanor may provide a new approach to [phosphorus] management in renal disease and associated mineral disorders,” the authors reported.

The second study investigated the effects of tenapanor on phosphorus absorption in healthy volunteers. Two double-blinded, placebo-controlled studies examined two dosing regimens over a 7-day period—multiple ascending dosing and different dosing.

Both regimens demonstrated increased phosphorus excretion for participants receiving the drug compared to placebo. “Tenapanor may provide a new mechanism for the treatment of hyperphosphatemia, with the potential added benefits of reducing pill burden and improving Na overload in patients with end stage renal disease,” the authors concluded.

Study authors acknowledged receiving funding from Ardelyx, Inc., and AstraZeneca.

Studies: “Tenapanor Inhibits Phosphorous Absorption, and Protects against Vascular Calcification in Nephrectomized Rats” (Abstract FR-OR111)

“Tenapanor, a Minimally Absorbed NHE3 Inhibitor, Reduces Dietary Phosphorus Absorption in Healthy Volunteers” (Abstract FR-OR112)

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ASN Kidney Week 2014, the largest nephrology meeting of its kind, will provide a forum for more than 13,000 professionals to discuss the latest findings in kidney health research and engage in educational sessions related to advances in the care of patients with kidney and related disorders. ASN Kidney Week 2014 will take place November 11–16, 2014, at the Pennsylvania Convention Center in Philadelphia, PA.

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Founded in 1966, and with nearly 15,000 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.# # #