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The investigational oral treatment difelikefalin (Korsuva) reduced pruritus in patients with chronic kidney disease (CKD) in a phase II trial.

Among 269 patients with moderate-to-severe CKD, 1 mg of difelikefalin significantly reduced itching intensity compared with placebo as measured by the daily 24-hour Worst Itching Intensity Numeric Rating Scale (-4.4 vs -3.3 placebo, P=0.018), reported Gil Yosipovitch, MD, of the University of Miami, and colleagues.

Meeting its primary efficacy endpoint, the was presented at the National Kidney Foundation's virtual Spring Clinical Meeting 2020.

A total of 37% of patients on 1 mg of difelikefalin achieved a complete treatment response versus only 14.3% of those on placebo by the end of the 12-week trial (P=0.006). And difelikefalin showed a statistically significant improvement in pruritus by only the second week of treatment, maintained through the end of the trial.

Difelikefalin works as a restricted, selective agonist at kappa opioid receptors to reduce pruritus.

"There is a significant unmet need in patients with chronic kidney disease-associated pruritus and there are no approved treatments in the U.S. and Europe," Yosipovitch and co-study author Ahmed Awad, DO, of Kansas City Kidney Consultants in Missouri, jointly explained to 番茄社区.

A phase III trial of an intravenous version of difelikefalin in hemodialysis patients already demonstrated significant reduction in itch intensity and improvement in itch-related quality of life, the pair noted.

"The goal of this study was to look beyond hemodialysis patients and evaluate an oral formulation of difelikefalin in a broader range of patients with stage 3-5 CKD including non-dialysis and dialysis patients with moderate to severe pruritus," they explained.

The trial included patients in these later stages of CKD with related moderate-to-severe pruritus, who were randomized equally to placebo or one of three doses of difelikefalin (0.25, 0.5, or 1 mg) once daily. Average baseline itching intensity scores were 7.1 and 7.0 in the active-drug groups and placebo group, respectively.

"The traditional thinking is that pruritus is more prevalent in severe CKD and patients undergoing hemodialysis. Surprisingly, about 60% of patients in this study had stage 3 CKD, confirming pruritus is prevalent across moderate to severe stages of CKD," Yosipovitch and Awad highlighted.

They noted that baseline itching scores were similar across patients with stage 3, 4, and 5 CKD, and was even similar between non-dialysis and dialysis patients. Of note, difelikefalin was efficacious at treatment pruritus regardless of CKD stage or dialysis status.

As for secondary endpoints, 72% of patients on 1 mg of difelikefalin were able to achieve at least a 3-point improvement in their weekly average itching score, only achieved by 58%. However, this difference wasn't statistically significant. And although more patients on 1 mg of treatment had greater quality-of-life improvements measured by the Skindex-10 and 5-D Itch scales when compared with placebo, this also wasn't statistically significant.

Among patients on difelikefalin, some of the most common adverse events that occurred in more than 5% of patients included dizziness (7.5% vs 0% of placebo), falling (6% vs 0%), diarrhea (6% vs 1.5%), and constipation (6% vs 3%).

"Although we need more data and further evaluation, difelikefalin is an emerging option which has shown promise in several clinical trials thus far," the trial authors concluded.

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