KALM-2 pivotal phase III trial of Korsuva shows efficacy in chronic kidney disease-associated pruritus.- Cara Therapeutics/Vifor Fresenius

Cara Therapeutics and Vifor Fresenius Medical Care Renal Pharma announced positive topline data from Cara’s KALM-2 pivotal Phase III trial of Korsuva (CR845/difelikefalin) Injection in hemodialysis patients with moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP). CKD-aP is an intractable systemic itch condition that occurs with high frequency and intensity in patients undergoing hemodialysis. Multiple studies estimate that at least 40% of dialysis patients suffer from pruritus.

For the primary endpoint, the proportion of patients on 0.5 mcg/kg of Korsuva Injection achieving a three-point or greater improvement from baseline in the weekly mean of the daily 24 hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) score at week 12 was 54% versus 42% for patients on placebo (p= 0.02). For the key secondary endpoint, the proportion of patients on 0.5 mcg/kg of Korsuva Injection achieving a four-point or greater improvement from baseline in the weekly mean of the daily 24 hour WI-NRS score at week 12 was 41% versus 28% for patients on placebo (p= 0.01).

For itch-related quality of life measures, patients on Korsuva Injection experienced a 12% and 29% numerical improvement in the average total Skindex-10 and total 5-D Itch scores, respectively, which did not meet statistical significance. Korsuva Injection was generally well-tolerated with a safety profile consistent with that seen in KALM-1 and the Korsuva clinical program in patients with CKD-aP.

Overall, the incidence of adverse events (AEs) and serious AEs were similar across both Korsuva and placebo groups. The most common treatment-emergent AEs reported in >5% of patients were diarrhea (8.1% Korsuva versus 5.5% placebo), falling (6.8% Korsuva versus 5.1% placebo), vomiting (6.4% Korsuva versus 5.9% placebo), nausea (6.4% Korsuva versus 4.2% placebo) and dizziness (5.5% Korsuva versus 5.1 % placebo).

The company is on track to submit a New Drug Application for Korsuva Injection in the second half of this year to the U.S. Food and Drug Administration (FDA) and, working with partner Vifor Fresenius Medical Care Renal Pharma, plan to submit for Marketing Authorization Approval (MAA) to the European Medicines Agency (EMA) shortly thereafter.