In a phase 3 randomized controlled trial, researchers found that intravenous anrikefon reduced itch severity and improved quality of life in patients with chronic kidney disease–associated pruritus undergoing hemodialysis. At week 12, 37% of patients receiving anrikefon achieved at least a 4-point reduction in itch scores compared with 15% in the placebo group. More than half of patients in the anrikefon group achieved a 3-point reduction compared with one quarter of placebo recipients. Improvements were observed as early as the second week and continued through week 12. Quality-of-life measures also favored anrikefon, with greater improvements in Skindex-10 and 5-D Itch scores.
In a subgroup analysis of age, researchers reported no statistically significant differences in the proportion of patients aged 65 years and older who achieved a 4-point reduction in itch scores between groups. Statistically significant differences were observed across all other age groups and in both sexes.
In a 40-week open-label extension, patients from both groups could continue with anrikefon treatment. At week 40, 356 of 443 participants showed persistent improvement in quality-of-life scores on the 5-D Itch scale. The researchers noted that the change from baseline during the double-blind phase was −7.8 points among the 176 patients who were originally assigned to anrikefon and −7.6 points among the 180 patients originally assigned to placebo.
Adverse events occurred in 83% of patients who received anrikefon and 82% of those who received placebo. Severe events were reported in 18% and 21%, respectively. Dizziness was the most common drug-related event with anrikefon and was generally mild to moderate. Three deaths occurred in the anrikefon group and five in the placebo group during the double-blind phase. In the 40-week open-label extension, adverse events occurred in 93% of patients, drug-related adverse events in 21%, and 20 deaths (4%) were reported overall. No dysphoria or hallucination events, which are well-documented with centrally acting kappa opioid receptor agonists occurred.
“Notably, anrikefon has a spiral ring structural modification, which improves the binding affinity of kappa opioid receptor, providing stronger agonistic activity,” wrote Jiang-Hua Chen, MD, of Zhejiang University School of Medicine, with colleagues. “An in vitro study revealed that the agonistic activity of anrikefon was more than 12 times higher than that of difelikefalin. Moreover, the treatment dose of anrikefon was lower than that of difelikefalin (0.3 μg/kg vs 0.5 μg/kg). Importantly, the present phase 3 trial showed that anrikefon’s efficacy with a lower treatment dose was comparable to that of difelikefalin (37.2% vs 37.1%) in treating pruritus in patients undergoing haemodialysis.”
The study enrolled 652 patients at 50 centers in China between June 2022 and June 2024. A total of 545 patients were randomized, with 275 assigned to anrikefon and 270 to placebo. Patients had moderate to severe pruritus while receiving thrice-weekly hemodialysis. Anrikefon was administered intravenously at 0.3 micrograms per kilogram three times weekly within 1 hour following dialysis, either through the dialysis circuit or intravenously in the arm. Randomization was stratified by baseline itch severity. The primary endpoint was the proportion of patients with at least a 4-point reduction in mean itch scores at week 12. Secondary endpoints included a 3-point reduction and changes in Skindex-10 and 5-D Itch scores. The trial permitted stable doses of antipruritic medications but did not allow initiation of new therapy following screening. Analyses included logistic regression for the primary endpoint and mixed-effects models for secondary outcomes.
Limitations included the single-country setting, which may affect generalizability, and the open-label design, which could have introduced bias in adverse-event reporting. Because only patients with end-stage renal disease undergoing hemodialysis were enrolled, the safety and efficacy of anrikefon in nondialysis-dependent chronic kidney disease should be evaluated. The researchers also noted that an active controlled trial comparing anrikefon with approved treatments is needed.
They concluded, "The sustained therapeutic effect and low incidence of central opioid adverse reactions make anrikefon a promising new treatment option for patients with CKD associated pruritus."
Full disclosures can be found in the study.
Source: The BMJ