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%; <.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%; <.001).


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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.

References

  1. 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. 
  2. Fishbane S, Jamal A, Munera C, et al. A phase 3 trial of difelikefalin in hemodialysis patients with pruritusN Engl J Med. 2020;382:222-232. doi:10.1056/NEJMoa1912770.
  3. 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.