The Food and Drug Administration has approved Korsuva™ (difelikefalin) injection for the treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis.
Korsuva is a kappa opioid receptor agonist that targets the peripheral nervous system. The approval was based on data from the pivotal phase 3 KALM-1 (ClinicalTrials.gov Identifier: NCT03422653) and KALM-2 trials (ClinicalTrials.gov Identifier: 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 in 851 patients 18 years of age and older undergoing hemodialysis who had moderate to severe pruritus. 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 efficacy endpoint for both studies was the proportion of patients with an improvement of at least 4 points from baseline at week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS).
Results from the KALM-1 trial showed that 40% of difelikefalin-treated patients had an improvement of at least 4 points in the WI-NRS score at week 12 compared with 21% for placebo (difference 19%; 95% CI, 9%-28%). In the KALM-2 trial, 37% of difelikefalin-treated patients achieved a 4-point or greater improvement in WI-NRS score vs 26% for placebo (difference 12%; 95% CI, 3%-20%). Itch reduction was by week 4 and sustained through week 12.
The most common adverse reactions reported with difelikefalin were diarrhea, dizziness, nausea, gait disturbances, including falls, hyperkalemia, headache, somnolence, and mental status change.
Korsuva is supplied as a single-dose vial containing 65mcg/1.3mL of difelikefalin as a sterile, preservative-free solution for intravenous injection. It is expected to be available in the US in the first quarter of 2022.
Korsuva has not been studied in patients on peritoneal dialysis and is not recommended in this population as well as in those with severe hepatic impairment.
- Vifor Pharma and Cara Therapeutics announce US FDA approval of Korsuva™ injection for the treatment of moderate-to-severe pruritus in hemodialysis patients. News release. Vifor Pharma and Cara Therapeutics. Accessed August 24, 2021. https://www.businesswire.com/news/home/20210823005635/en/Vifor-Pharma-and-Cara-Therapeutics-announce-U.S.-FDA-approval-of-KORSUVA%E2%84%A2-injection-for-the-treatment-of-moderate-to-severe-pruritus-in-hemodialysis-patients.
- Korsuva [package insert]. Stamford, CT: Cara Therapeutics, Inc.; 2021.