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The FDA approved difelikefalin (Korsuva) on Monday for treating pruritus in chronic kidney disease (CKD) patients, .

Difelikefalin is a first-in-class kappa opioid receptor (KOR) agonist that targets the peripheral nervous system, according to the two companies. Administered as an injection (0.5 μg/kg three times per week), the drug is indicated for moderate-to-severe pruritus in CKD patients on hemodialysis -- the first therapy approved in this setting.

Support for the approval came primarily from two phase III trials -- KALM-1, a double-blind placebo-controlled trial conducted at 56 sites across the U.S., and KALM-2, an international trial.

In KALM-1, which involved 378 CKD patients with moderate-to-severe pruritus who were undergoing hemodialysis, 49.1% of those assigned to difelikefalin had at least a 3-point decrease on the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS) by week 12, as compared with 27.9% of those assigned to placebo (P<0.001), meeting the study's primary endpoint.

By that same time point, twice as many patients on the study drug had at least a 4-point improvement in their WI-NRS score (a 10-point scale) versus those on placebo (37.1% vs 17.9%, P<0.001), according to the findings published in the .

The KOR agonist also led to significant improvements in itch-related quality of life on the Skindex-10 and 5-D itch scales.

"Participating in the robust clinical trial program we have learned that Korsuva injection represents an effective treatment option," said Frank Maddux, MD, CEO of Fresenius Medical Care, in a statement from the drugmakers. "We have seen substantial improvement in symptoms and meaningful relief for people suffering from severe and debilitating itch."

Common adverse events (AEs) with difelikefalin recorded in the KALM trials (and that were more frequent than with placebo) included diarrhea in 9%; dizziness, nausea, and gait disturbances such as falls in 7% each; hyperkalemia and headache in 5%; somnolence in 4%; and mental status changes in 3%.

Use in combination with opioids, centrally acting depressants, and sedating antihistamines could increase the likelihood of certain AEs. Patients undergoing treatment with difelikefalin should be advised not to operate machinery or drive a car while on treatment, until the drug's effects on their mental and physical abilities are established.

The drug has not been studied and is not recommended for use in patients on peritoneal dialysis, the drugmakers noted. Also, the drug has not been evaluated among patients with severe liver impairment.

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