The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for difelikefalin (Korsuva™; Cara Therapeutics), a kappa opioid receptor agonist, for the treatment of moderate to severe pruritus in hemodialysis patients.
The NDA submission is supported by data from the pivotal phase 3 KALM-1 (ClinicalTrials.gov: NCT03422653) and KALM-2 trials (ClinicalTrials.gov: NCT03636269), as well as data from an additional 32 clinical studies. The KALM-1 and KALM-2 trials evaluated the efficacy and safety of difelikefalin for chronic kidney disease-associated pruritus in hemodialysis patients 18 years of age and older. Patients were randomly assigned to receive difelikefalin 0.5mcg/kg intravenously 3 times per week after each dialysis session or placebo for 12 weeks.
The primary end point for both studies was the proportion of patients with an improvement of at least 3 points from baseline at week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS). A key secondary end point included the proportion of patients with an improvement of at least 4 points in the WI-NRS score at week 12.
Results from the KALM-1 trial showed a significantly greater proportion of patients in the difelikefalin treatment arm had a decrease of at least 3 points in the WI-NRS score compared with placebo (49.1% vs 27.9%; P <.001). Additionally, a greater proportion of difelikefalin-treated patients had an improvement of at least 4 points in the WI-NRS score at week 12 compared with placebo (37.1% vs 17.9%; P <.001).
In the KALM-2 trial, the proportion of patients achieving a 3-point or greater improvement in the WI-NRS score was 54% for difelikefalin vs 42% for placebo (P =.02). Moreover, 41% of difelikefalin-treated patients achieved a 4-point or greater improvement in WI-NRS score compared with 28% for placebo (P =.01).
As for safety, difelikefalin was generally well tolerated with the most common treatment-emergent adverse events being diarrhea, vomiting, nausea, and dizziness.
A Prescription Drug User Fee Act (PDUFA) target date of August 23, 2021 has been set for this application.
- Vifor Pharma and Cara Therapeutics announce U.S. FDA acceptance and Priority Review of NDA for Korsuva™* injection in hemodialysis patients with moderate-to-severe pruritus. [press release]. St. Gallen, Switzerland and Stamford, CT: Vifor Pharma and Cara Therapeutics, Inc; March 8, 2021.
- Fishbane S, Jamal A, Munera C, et al. A phase 3 trial of difelikefalin in hemodialysis patients with pruritus. N Engl J Med. 2020;382:222-232. doi:10.1056/NEJMoa1912770.
- Cara Therapeutics and Vifor Fresenius Medical Care Renal Pharma announce positive results from global KALM-2 pivotal phase 3 trial of KorsuvaTM injection in hemodialysis patients with pruritus. [press release]. St. Gallen, Switzerland and Stamford, CT: Vifor Pharma and Cara Therapeutics, Inc; April 21, 2020.