Breakthrough Pruritus Therapy Reaches Phase 3 Clinical Endpoint

- Apr 22, 2020-

On the 22nd, Cara Therapeutics and Vifor Fresenius Medical Care Renal Pharma (VFMCRP) jointly announced that Korsuva (CR845 / difelikefalin) injection developed by Cara is used to treat hemodialysis patients with moderate to severe chronic kidney disease-related pruritus (CKD-aP) In the critical phase 3 trial KALM-2, positive top-line data was obtained. Korsuva is a peripheral κ opioid receptor agonist. Cara and VFMCRP are expected to submit Korsuva's New Drug Application (NDA) in the second half of this year.

CKD-aP is a refractory, systemic pruritus that occurs mostly in CKD patients undergoing hemodialysis and peritoneal dialysis. Itching can also occur in patients with stage III-V CKD who have not received dialysis treatment. Comprehensive longitudinal multi-country studies have estimated that the weighted prevalence of CKD-aP in patients with end-stage renal disease is about 40%, and about 25% of patients will develop severe pruritus. About 60% -70% of dialysis patients will develop pruritus, of which 30% to 40% are moderate to severe pruritus. The main treatment regimens currently used for these patients are antipruritic treatments, such as antihistamines and corticosteroids, but they do not provide consistent and adequate relief. Moderate to severe chronic itching can directly affect the patient's quality of life, such as poor sleep quality, and may even cause depression.

Korsuva is a highly selective peripheral κ opioid receptor agonist. Korsuva has potent analgesic, anti-inflammatory and anti-itching properties in both humans and animals. Because Korsuva performs poorly at penetrating the blood-brain barrier, it has little or no CNS-mediated side effects such as nausea, vomiting, sedation, respiratory depression, abuse, addiction, or euphoria. This innovative research-in-progress therapy was awarded the breakthrough therapy certification by the US FDA in 2017.

KALM-2 is a multi-center, randomized, double-blind, phase 3 clinical trial with a placebo control group. It aims to evaluate the safety and effectiveness of Korsuva injection in the treatment of 473 patients with moderate to severe CKD-aP hemodialysis. The trial data showed that in the 12th week of treatment, 54% of the patients in the treatment group had a 24-hour daily itching intensity digital rating scale (WI-NRS) score of 3 points or more, which was achieved in the placebo group. The proportion of patients at level 1 was 42%, reaching the primary study endpoint of the trial. In addition, 41% of patients in the treatment group improved their WI-NRS score by 4 points or more from baseline, and only 28% of patients in the placebo group reached this level, reaching the key secondary endpoint of the trial.

"We are very pleased with the positive top-line data obtained from the Phase 3 clinical trial of Korsuva injection, which further proves the positive results obtained from the KALM-1 trial," said Dr. Derek Chalmers, President and CEO of Cara Therapeutics: "These data Will support us to submit new drug applications for Korsuva injection to the US FDA in the second half of this year, and support our partner VFMCRP to submit Korsuva's marketing authorization application to the European Medicines Agency (EMA). "