WASHINGTON, DC — The intensity of itch experienced by patients on hemodialysis with uremic pruritus can be eased with 12 weeks of treatment with difelikefalin (Korsuva, Cara Therapeutics), results from the phase 3 KALM-1 study show.
"For the first time in my career, which has been filled with negative studies trying to improve uremic pruritus," we have a drug "that was effective and well tolerated," said investigator Steven Fishbane, MD, from Northwell Health in Great Neck, New York.
This is a really difficult-to-treat population of patients. Difelikefalin comes in on "what, right now, is a blank space. There just isn't anything that we have that works well in this regard," he said during a news conference here at Kidney Week 2019.
The study was also simultaneously published in the New England Journal of Medicine.
It is estimated that at least 40% of patients with end-stage renal disease suffer from pruritus. Currently, the only approved treatment is an antihistamine, such as Benadryl. Ultraviolet light therapy also helps, but having patients go for light therapy on top of doing dialysis 3 days a week is simply a lot to ask, said Fishbane, who has served as a consultant for and received research fees from Cara Therapeutics.
Uremic pruritus is a significant problem for many patients on hemodialysis, and it clearly affects their quality of life, said Pascale Lane, MD, from the University of Oklahoma Health Sciences Center in Oklahoma City, who chaired the news conference.
"This is the first agent I know of that has shown any efficacy in this condition," she told Medscape Medical News.
"And while we do give Benadryl to our patients on dialysis, I don't know how much it stops the itching or if it's just sedating the patient," she added.
Because difelikefalin is a kappa opioid receptor agonist — it does not touch the mu receptor in the brain — there is no potential for abuse. There is no euphoria and no withdrawal symptoms, he explained.
The multicenter, double-blind, placebo-controlled KALM-1 study, conducted in 56 centers in the United States, involved 377 patients with pruritus related to chronic kidney disease and was supported by Cara Therapeutics.
The degree of itching experienced by each study participant was established during an initial 7-day run-in period. Half the participants were randomized to difelikefalin 0.5 μg/kg administered intravenously 3 times a week for 12 weeks, and half were randomized to placebo.
The drug, which stays in the system for 2 to 3 days, is eliminated with dialysis so it is re-administered after each session.
The study was designed to assess the effect of the drug on symptoms, "using highly validated surveys," Fishbane said.
At week 12, more patients in the difelikefalin group than in the placebo group had achieved an improvement of at least 3 points on the Worst Itch Numeric Rating Scale (WI-NRS) from baseline (51% vs 28%; P < .001).
An improvement of at least 4 points — which they like to use in the dermatology world, Fishbane explained — was also significantly more likely with difelikefalin than with placebo (39% vs 18%; P < .001).
Itch-related quality-of-life at 12 weeks was 35% better with difelikefalin than with placebo when measured with the 5-D Itch Scale (P < .001), and was 43% better when measured with Skindex-10 (P < .001).
"The drug was generally well tolerated," Fishbane reported. There was a slight elevation in transient diarrhea, dizziness, and nausea in the difelikefalin group, but otherwise, adverse-event profiles were comparable in the two groups.
"These results suggest that, if approved, difelikefalin will be an important drug that could help many of our patients," he said.
The fact that difelikefalin can be infused after a patient is finished with dialysis is also a very attractive aspect of the treatment, Lane added. "Anything we can find that you give after dialysis and that lasts until the next treatment, well, that's just a piece of cake."
Kidney Week 2019: American Society of Nephrology Annual Meeting: Abstract FR-OR134. Presented November 8, 2019.
N Engl J Med. Published online November 8, 2019. Abstract
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Cite this: New Option for Difficult-to-Treat Uremic Pruritus - Medscape - Nov 11, 2019.