Kidney Week

Abstract: PO1136

RDX013, a Novel, Oral, Small Molecule Being Developed for Treatment of Hyperkalemia, Increases Colonic Secretion and Fecal Excretion of Potassium

Session Information

• Salt, Potassium, and Water Balance: Clinical
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolyte, and Acid-Base Disorders

• 902 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

• Kozuka, Kenji, Ardelyx Inc, Fremont, California, United States

Kenji Kozuka

• Siegel, Matthew, Anwita Biosciences, San Carlos, California, United States

Matthew Siegel,

• King, Andrew J., Chinook Therapeutics Inc, Vancouver, British Columbia, Canada

Andrew J. King,

• Kohler, Jill N., Ardelyx Inc, Fremont, California, United States

Jill N. Kohler,

• Jiang, Zhengfeng, Ardelyx Inc, Fremont, California, United States

Zhengfeng Jiang,

• Quach, Allison, Ardelyx Inc, Fremont, California, United States

Allison Quach,

• Fung, Cyra, Ardelyx Inc, Fremont, California, United States

Cyra Fung,

• He, Ying, Ardelyx Inc, Fremont, California, United States

Ying He,

• Kumaraswamy, Padmapriya, Ardelyx Inc, Fremont, California, United States

Padmapriya Kumaraswamy,

• He, Limin, Ardelyx Inc, Fremont, California, United States

Limin He,

• Le, Cathy Mai Uyen, Ardelyx Inc, Fremont, California, United States

Cathy Mai Uyen Le,

• Tran, Catarina, Ardelyx Inc, Fremont, California, United States

Catarina Tran,

• Caldwell, Jeremy, Inception Therapeutics, San Diego, California, United States

Jeremy Caldwell,

• Rosenbaum, David P., Ardelyx Inc, Fremont, California, United States

David P. Rosenbaum,

• Jacobs, Jeffrey, Ardelyx Inc, Fremont, California, United States

Jeffrey Jacobs,

Background

Potassium (K⁺) homeostasis is maintained by the balance of dietary K⁺ intake, extra- and intracellular K⁺ distribution, and renal and intestinal excretion. Hyperkalemia (serum K⁺>5.0 mM) occurs frequently in CKD patients and can lead to cardiac arrhythmias and sudden death; controlling serum K⁺ may reduce mortality in this population. Current therapeutic options for the chronic treatment of hyperkalemia are limited to K⁺-binding agents. Here, we describe the discovery of RDX013, a novel, oral, small molecule K⁺ secretagogue in development for treatment of hyperkalemia.

Methods

Male Sprague Dawley rats (n=6/group) were orally administered vehicle or 6 mg/kg RDX013 twice daily for 6 days. 24-hour fecal samples collected from rats housed individually in metabolic cages on the final study day were homogenized, and K⁺ and sodium were analyzed by cation exchange chromatography.

Results

RDX013 significantly increased fecal K⁺ excretion compared to vehicle control animals (figure). Fecal sodium was also increased by RDX013 (figure), which was expected as luminal sodium retention in the intestine is key to the pharmacodynamic response.

Conclusion

Based on its unique mechanism of action which involves pharmacologically enhancing K⁺ secretion through apical K⁺ channels in the colon, RDX013 is a potential first-in-class therapy which may provide a new approach to managing serum K⁺ in patients versus commonly prescribed K⁺ binders. A phase 2 clinical study with RDX013 (NCT04780841) is ongoing in non-dialysis CKD patients with hyperkalemia.

Funding

• Commercial Support –