Positive data from KALM-1 pivotal Phase III trial of Korsuva in hemodialysis patients with moderate-to-severe chronic kidney disease-associated pruritus.

Cara Therapeutics, Inc. a biopharmaceutical company focused on developing and commercializing new chemical entities with a primary focus on the treatment of pruritus by selectively targeting peripheral kappa opioid receptors, announced positive topline data from the KALM-1 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 and peritoneal dialysis. Multiple studies estimate that at least 40 percent of patients with end-stage renal disease suffer from pruritus. The FDA has granted Breakthrough Therapy designation to Korsuva Injection for this indication. “Itching is a significant problem for many of our hemodialysis patients and there is an unmet need for an effective treatment. I am impressed by the clinically meaningful efficacy demonstrated in this study,” said Steven Fishbane, M.D., Chief, Division of Kidney Disease and Hypertension, Northwell Health, Professor of Medicine at Hofstra/Northwell and a KALM-1 clinical investigator. “Relative to the favorable safety data, these results suggest that, if approved, this can be an important drug that could help many of our patients.” KALM-1 Efficacy Data: 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 51% vs. 28% for patients on placebo (p= 0.000019). Secondary Endpoints: 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 39% vs. 18% for patients on placebo (p= 0.000032). Itch-Related Quality of Life Measures: The impact of Korsuva Injection on itch-related quality of life measures associated with CKD-aP was measured using validated self-assessment Skindex-10 and 5-D itch scales: Patients on Korsuva Injection experienced a 43% improvement in the average total Skindex-10 score at week 12 vs. patients on placebo (p= 0.0004). Patients on Korsuva Injection experienced a 35% improvement in the average total 5-D Itch score at week 12 vs. patients on placebo (p= 0.0009) KALM-1 Safety and Tolerability: Korsuva was generally well-tolerated with a safety profile consistent with that seen in earlier Korsuva clinical trials. 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 (9.5% Korsuva vs 3.7% placebo), dizziness (6.9% Korsuva vs 1.1% placebo), nasopharyngitis (Korsuva 5.3% vs 3.2% placebo) and vomiting (5.3% Korsuva vs 3.2% placebo).