Kidney Week

Abstract: TH-PO448

Randomized Controlled Trial of Long-Term Safety and Efficacy of Veverimer for Treatment of Metabolic Acidosis

Session Information

• CKD: Clinical, Outcomes, Trials - I
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Wesson, Donald E., Baylor Scott and White Health and Wellness Center, Dallas, Texas, United States

Donald E. Wesson,

• Mathur, Vandana S., Mathur Consulting, Woodside, California, United States

Vandana S. Mathur,

• Tangri, Navdeep, University of Manitoba, Ottowa, Manitoba, Canada

Navdeep Tangri,

• Stasiv, Yuri, Tricida, Inc., South San Francisco, California, United States

Yuri Stasiv,

• Parsell, Dawn, Tricida, Inc., South San Francisco, California, United States

Dawn Parsell,

• Li, Elizabeth, PharmaStat, LLC, Newark, California, United States

Elizabeth Li,

• Klaerner, Gerrit, Tricida, Inc., South San Francisco, California, United States

Gerrit Klaerner,

• Bushinsky, David A., University of Rochester Medical Center, Rochester, New York, United States

David A. Bushinsky,

Background

Metabolic acidosis in CKD is associated with accelerated GFR decline, augmented muscle catabolism and increased mortality. Veverimer, an oral, non-absorbed, counterion-free, polymeric drug candidate, selectively binds and removes HCl from the GI lumen.

Methods

We report a multicenter, randomized, blinded, placebo-controlled, 40-wk extension (n=196) of a 12-wk parent study (n=217) in patients with CKD (eGFR 20-40 mL/min/1.73m²) and metabolic acidosis (serum bicarbonate 12-20 mEq/L) randomly assigned (4:3) to veverimer or placebo. The primary endpoint was safety; secondary endpoints were effect on bicarbonate level, patient-reported physical function (Kidney Disease and Quality of Life Physical Functioning Domain [KDQOL-PFD] and objectively measured physical function (repeated chair stand [RCS] test). A pre-specified time to event analysis for the composite outcome of death, RRT or eGFR decline >50% was also performed.

Results

Fewer patients on veverimer than placebo discontinued treatment prematurely (2.6% vs 9.8%) or experienced a serious adverse event (1.8% vs. 4.9%). No patients on veverimer died (vs. 2 on placebo) or discontinued due to an adverse event (vs. 1 on placebo) and the frequencies of common adverse events were comparable between groups. More patients on veverimer than placebo had an increase in bicarbonate (>4 mEq/L or normalization) at Week 52 (62.7% vs. 37.8%, p=0.001) and higher bicarbonate levels were observed on veverimer at all time points (p<0.001). The KDQOL-PFD score improved on veverimer vs. placebo, with a mean placebo-subtracted (SE) change at end of treatment of 12.1 (3.3) points (p<0.0001). Veverimer specifically improved ability to climb 1 flight of stairs (p<0.0001) and all measures of walking (p<0.01) on the KDQOL-PFD. Time to perform the RCS test decreased by 4.3 (1.2) sec on veverimer vs. 1.4 (1.2) sec on placebo (p<0.0001). Veverimer was associated with longer time to the kidney composite endpoint (annualized incidence rate 4.2% [veverimer] vs. 12.0% [placebo], p=0.022).

Conclusion

Veverimer safely and effectively improved metabolic acidosis in patients with CKD. Our multicenter, randomized, controlled trial adds to the evidence that treating metabolic acidosis slows progression of CKD and improves physical function.

Funding

• Commercial Support –