The primary endpoint of the trial was a three-point or greater improvement from baseline on the daily 24 hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) score at week 12. In the trial, the score was 51% compared to 28% for patients receiving placebo.
Stamford, Conn.-based Cara Therapeutics announced positive topline results from its KALM-1 Phase III trial of Korsuva (CR845/difelikefalin) Injection in hemodialysis patients with moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP). Pruritus is systemic itching. It affects about 60-70% of patients with end-stage renal disease, with about 40% citing it as severe.
The primary endpoint of the trial was a three-point or greater improvement from baseline on the daily 24 hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) score at week 12. In the trial, the score was 51% compared to 28% for patients receiving placebo.
Secondary endpoints included proportion of patients receiving Korsuva finding a four-point or greater improvement from baseline in the weakly mean of the daily 24 WI-NRS score at week 12, which was 39% compared to 18% on the placebo cohort. And another secondary endpoint was impact on itch-related quality of life measures using validated self-assessment Skindex-10 and 5-D Ich scales. In this case, patients on Korsuva had a 43% improvement on Skindex-10 at week 12 compared to patients on placebo and a 35% improvement on the 5-D Itch score at 12 weeks compared to the placebo cohort.
The drug was generally well-tolerated and had a safety profile consistent with earlier Korsuva clinical trials. The incidence of adverse events was similar across the Korsuva and placebo groups. The most commonly reported were diarrhea, dizziness, nasopharyngitis and vomiting.
The KALM-1 Phase III trial is a multicenter, randomized, double-blind, placebo-controlled 12-week trial with a one-year (52-week) open label extension phase. It evaluated 0.5 mcg/kg Korsuva in 350 hemodialysis patients with moderate-to-severe pruritus.
“Itching is a significant problem for many of our hemodialysis patients and there is an unmet need for an effective treatment,” stated Steven Fishbane, Chief, Division of Kidney Disease and Hypertension, Northwell Health, Professor of Medicine at Hofstra/Northwell and a KALM-1 clinical investigator. “I am impressed by the clinically meaningful efficacy demonstrated in this study. 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.”
The company launched another open-label safety trial of Korsuva Injection that will enroll up to 400 hemodialysis patients with CKD-aP for up to 12 weeks of therapy. It also is enrolling patients in the Phase II trial of Oral Korsuva for pruritis in moderate-to-severe chronic kidney disease patients. Cara expects top-line data from the trial in the second half of this year.
At the company’s first-quarter financial results on May 7, Cara reported a net loss of $22 million and total revenue of $4.4 million, which came from license and milestone payments of $4.2 million from Vifor Fresenius Medical Care Renal Pharma and clinical compound revenue of $140,000 from the sale of a clinical compound to Maruishi Pharmaceutical.
R&D expenses were $23.6 million for the quarter, up from $13.4 million in the same period the year before. The higher R&D expenses were mostly related to clinical trial costs, as well as increases in stock compensation expense and payroll and related costs.
The company reported cash and cash equivalents and marketable securities of $156.1 million as of March 31, 2019. The company believes this will be enough to fund operations into the fourth quarter of 2020.
