Top-line data from Tricida’s VALOR-CKD trial showed veverimer failed to meet its primary endpoint and does not slow progression in patients with metabolic acidosis and CKD.
Top-line data from Tricida‘s VALOR-CKD Phase III trial released Monday showed veverimer failed to meet its primary endpoint and did not slow progression in patients with metabolic acidosis and chronic kidney disease (CKD).
In response to the news, Tricida’s shares plummeted around 94% Monday in pre-market trading.
VALOR-CKD evaluated veverimer’s ability to delay the occurrence of any of the following events: renal death, end-stage renal disease or a 40% minimum drop in estimated glomerular filtration rate. This composite outcome arose in 149 patients treated with Tricida’s candidate and 148 placebo counterparts. The resulting hazard ratio was 0.99 and had a p-value of 0.898.
“Ultimately, the analysis of serum bicarbonate data from the trial show that the trial did not compare an untreated acidotic population with a veverimer-treated population,” Gerrit Klaerner, Ph.D., chief executive officer and president of Tricida, said in an investor call Monday morning.
Because bicarbonate levels in placebo participants were in the normal range, the trial “thus was unable to assess veverimer’s ability to slow CKD progression by treating metabolic acidosis,” he added.
An Unexpected Failure
With nearly 2,200 patients enrolled, VALOR-CKD was a randomized, double-blinded and placebo-controlled trial that occurred in two phases.
The first was a single-blinded active-treatment period lasting for four to eight weeks. After veverimer treatment, patients who demonstrated at least a 4-mEq/L increase in their serum bicarbonate levels and those whose serum bicarbonate levels normalized were eligible for the next phase.
In the second part of VALOR-CKD, eligible patients were randomly assigned to continue veverimer treatment or switch to placebo. Almost 1,500 patients satisfied the serum bicarbonate criterion and participated in the trial’s second part.
Based on prior trials of veverimer, Tricida expected a stronger active treatment effect in the first phase of the trial. The company anticipated that around 74% of the participants would clear the serum bicarbonate threshold and that veverimer would induce an approximately 6-mEQ/L increase in the concentrations of this biomarker.
However, only 67% of participants ended up eligible for VALOR-CKD’s second part, and active treatment induced a serum bicarbonate increase of 4 mEq/L. After three months of treatment in the study’s placebo-controlled phase, the average serum levels of bicarbonate were 22 and 21 mEq/L in the veverimer and placebo arms, respectively. These levels were maintained for the majority of the study.
“In the VALOR-CKD trial, at each of the 3-month time points between month 3 and month 30 in part B, approximately 60% of the patients in the placebo group had a level of serum bicarbonate above 20 mEq/L,” Klaerner told investors. “The difference in serum bicarbonate levels between the two treatment groups was insufficient to evaluate the effect of veverimer on slowing CKD progression by treating metabolic acidosis.”
Because VALOR-CKD had already failed to reach its primary endpoint, Tricida could no longer conduct statistical analyses on the study’s secondary endpoints.
Tricida demonstrated a safety profile consistent with what is expected in patients with stage 3 to 5 CKD. All-cause death, cardiovascular death and serious adverse events all occurred at rates comparable between the veverimer and placebo arms.
Regarding the company’s next steps, Klaerner stated that the team is still currently coming to terms with VALOR-CKD’s data.
