• 1.

    Wesson DE, et al. Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial. Lancet 2019; 393:14171427. doi: 10.1016/S0140-6736(18)32562-5

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  • 2.

    Tricida, Inc. Evaluation of Effect of TRC101 on Progression of Chronic Kidney Disease in Subjects with Metabolic Acidosis (VALOR-CKD). ClinicalTrials.gov: NCT03710291. https://clinicaltrials.gov/ct2/show/NCT03710291

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  • 3.

    International Society of Nephrology. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3:1150. https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf

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Does Veverimer Hold the Future for Metabolic Acidosis?

  • 1 Katherine Kwon, MD, FASN, is a partner with Lake Michigan Nephrology in St. Joseph, MI.
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Veverimer is a novel agent for the treatment of metabolic acidosis in chronic kidney disease (CKD). It is a nonabsorbable polymer that selectively binds hydrochloric acid, leading to excretion of excess acid via the gastrointestinal tract. Veverimer completed a phase 3 clinical trial, demonstrating correction of serum bicarbonate when compared to placebo (1). However, in August 2020, the US Food and Drug Administration (FDA) declined to approve veverimer, requesting additional information on the likelihood of clinical benefit. This prompted manufacturer Tricida to create the VALOR-CKD trial. This ongoing trial will evaluate veverimer’s efficacy against placebo on progression of kidney disease (2).

Metabolic acidosis in CKD is associated with a wide range of deleterious effects, including impaired muscle function, decreased bone density, and accelerated progression to end-stage kidney disease. The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for management of CKD recommend treating metabolic acidosis with supplemental bicarbonate (3). However, bicarbonate and citrate (which metabolizes to bicarbonate) formulations include cations, such as sodium, potassium, or calcium, all of which can pose potential challenges in kidney patients who take them in large doses.

Veverimer allows for the correction of metabolic acidosis without the risks of the exogenous cations. It remains to be seen, however, if this correction leads to clinically meaningful outcomes for kidney patients. The VALOR-CKD trial seeks to answer this question but as a placebo-controlled trial, will not test efficacy against the current therapies in use. Existing therapies (sodium bicarbonate) are supported by several trials (albeit small) but do not have specific FDA approval for treating metabolic acidosis in CKD. Without a head-to-head trial, nephrologists and patients with kidney disease will need to decide if the anticipated extra cost of veverimer is worth it.

The author reports no conflict of interest.

References

  • 1.

    Wesson DE, et al. Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial. Lancet 2019; 393:14171427. doi: 10.1016/S0140-6736(18)32562-5

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Tricida, Inc. Evaluation of Effect of TRC101 on Progression of Chronic Kidney Disease in Subjects with Metabolic Acidosis (VALOR-CKD). ClinicalTrials.gov: NCT03710291. https://clinicaltrials.gov/ct2/show/NCT03710291

    • Search Google Scholar
    • Export Citation
  • 3.

    International Society of Nephrology. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3:1150. https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf

    • Search Google Scholar
    • Export Citation
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