Kidney Week

Abstract: SA-PO243

Combination Oxylanthanum Carbonate and Tenapanor Lowers Urinary Phosphate Excretion in Rats

Session Information

• CKD-MBD: Basic and Translational
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 501 Bone and Mineral Metabolism: Basic

Authors

• Medicherla, Satya, Unicycive Therapeutics Inc, Los Altos, California, United States

Satya Medicherla, PhD

• Reddy, Guru, Unicycive Therapeutics Inc, Los Altos, California, United States

Guru Reddy, PhD

• Gupta, Pramod, Unicycive Therapeutics Inc, Los Altos, California, United States

Pramod Gupta, PhD

• Chertow, Glenn M., Stanford University School of Medicine, Palo Alto, California, United States

Glenn M. Chertow, MD, MPH, FASN

• Gupta, Shalabh, Unicycive Therapeutics Inc, Los Altos, California, United States

Shalabh Gupta, MD

Background

End-stage kidney disease(ESKD) affects >7 million people worldwide and ~70% of patients with ESKD have hyperphosphatemia. Tenapanor, sodium/hydrogen exchanger(NHE3) inhibitor, reduces paracellular phosphate(P) absorption by inducing conformational changes in intestinal epithelium. Oxylanthanum carbonate(OLC) is an investigational new drug being developed for treatment of hyperphosphatemia under FDA’s 505(b)(2) regulatory pathway. If approved, OLC will share substantially the same product label and prescribing information as reference-listed drug Fosrenol^®(lanthanum carbonate), although OLC tablets are smaller in size and swallowed whole with water and not chewed. This study evaluated effects of OLC+tenapanor on urinary P excretion in rats on a high phosphorus diet.

Methods

64 male Sprague Dawley rats were fed standard chow 1 week prior to study start and then spiked with additional 0.4% inorganic phosphate [1:1 sodium:potassium salt, 1.1%(wt/wt) total phosphate content] for rest of the study. On study Day -1, animals were randomized into 8 groups(n=8 in each): 1) vehicle, 2) tenapanor 0.15mg/kg, 3) vehicle+OLC 0.75%, 4) vehicle+OLC 1.5%, 5) vehicle+OLC 3%, 6) OLC 0.75%+tenapanor 0.15mg/kg, 7) OLC 1.5%+tenapanor 0.15mg/kg, and 8) OLC 3%+tenapanor 0.15mg/kg. Vehicle and tenapanor were dosed PO twice daily whereas OLC was incorporated into the diets. 24-hour urine samples were collected using metabolic cages on day 9, 10, and 11 for urinary P measurements. OLC efficacy data are presented as average of all OLC doses(0.75%, 1.5%, and 3%).

Results

In tenapanor alone and OLC only groups, urinary P excretion was 8.5 and 12.0mg/day lower, respectively, compared to vehicle. In OLC+tenapanor groups, urinary P excretion was 28mg/day lower compared to vehicle.

Conclusion

Combination OLC+tenapanor demonstrates more pronounced P reduction than either agent used alone. The magnitude of P lowering suggests effect of OLC+tenapanor is synergistic rather than additive.

Funding

• Commercial Support – Unicycive Therapeutics, Inc.