Difelikefalin may offer dialysis patients some relief from the persistent itching associated with chronic dialysis, according to results from the KALM-1 trial presented during Kidney Week 2019.
The results were presented at the High Impact Clinical Trials session. Other trials presented during the session showed that azathioprine (AZA) may provide equivalent immunosuppression at a fraction of the price of mycophenolate mofetil (MMF), while vitamin D and omega-3 fatty acids failed to offer kidney protection for patients with diabetes.
Itching has proven to be a difficult-to-treat side effect of dialysis despite its substantial impact on patients’ quality of life and mortality, said Steven Fishbane, MD, chief of nephrology at Northwell Health in Manhasset, New York. In fact, he noted he’s seen negative trial result after negative trial result throughout his career. Currently, antihistamines are commonly used along with moisturizers or ultraviolet light therapy, Fishbane said. He said light therapy can work well but it adds to a patient’s treatment burden.
“When you have [itching] chronically, it is a very tough sentence that affects quality of life,” Fishbane said. “[It affects] sleep quality and is actually associated with infections, decreased erythropoietin response, and even mortality.”
But Fishbane was buoyed by the promising results he presented from the KALM-1 trial. The phase 3 trial randomized 377 patients to receive intravenous difelikefalin or placebo after dialysis 3 times per week for 12 weeks. The trial met both its primary and secondary endpoints, with 51% of patients in the difelikefalin arm achieving a 3-point or greater reduction in itching intensity based on the Worst Itching Intensity Numerical Rating Scale (WI-NRSA) compared with 28% of the placebo group at 12 weeks, and 39% of the treatment group achieving a 4-point or greater reduction in WI-NRSA compared to 18% of the placebo group. He noted that patients were about 3 times more likely to experience a clinically meaningful reduction in itching in the difelikefalin group. Serious adverse events were similar between the 2 groups, but patients on difelikefalin were more likely to have diarrhea (9.5% vs. 3.7%), dizziness (6.9% vs. 1.1%), or vomiting (5.3% vs. 3.2%), but these symptoms resolved after a short time.
“We’ve got the first drug available to be able to treat uremic pruritis,” Fishbane said. “The drug was effective. The drug was well tolerated in this really difficult population of patients with hemodialysis.”
“This is a wonderful development,” said Pascale Lane, MD, a pediatric nephrologist at the University of Oklahoma Medicine in Oklahoma City. She noted that in addition to demonstrating improved quality of life, the drug is convenient. “It can be given at the end of treatment when we’ve already got vascular access ready and it hangs around until they get dialyzed again,” she said.
“Efficacy and Safety of Difelikefalin in Patients Undergoing Hemodialysis with Pruritus: Results from a Phase 3 Randomized, Controlled Study (KALM-1)” Oral Abstract 134