Difelikefalin (Korsuva): Uses, Evidence, and Side Effects

Key takeaways

• Difelikefalin, sold as Korsuva, is approved specifically for itch tied to chronic kidney disease in adults on hemodialysis.
• It works by activating kappa opioid receptors, though the label notes the exact link to its therapeutic effect is not established.
• It is not recommended for patients on peritoneal dialysis because it has not been studied in that group.
• More than 20 registered trials have examined the drug, including two completed Phase 3 studies in hemodialysis patients.
• Reported adverse events most often involve the nervous system, including dizziness, somnolence, and falls.

What Difelikefalin Is

Difelikefalin is a kappa opioid receptor (KOR) agonist, a type of drug that targets opioid receptors associated with pain and itch signaling. According to its label, the relevance of this receptor activation to how well the drug works is not fully known. The compound has a molecular formula of C36H53N7O6.

What Difelikefalin Is Approved For

Marketed as Korsuva, difelikefalin is approved to treat moderate-to-severe pruritus, or itching, linked to chronic kidney disease in adults who are undergoing hemodialysis. This condition is often referred to as CKD-aP. The label specifies that Korsuva has not been studied in people on peritoneal dialysis and is not recommended for that population. No boxed warning is listed for this drug.

What the Evidence Shows

Difelikefalin has been studied across 23 registered clinical trials. Among them, the KALM-1 study and the CR845-CLIN3105 study were both completed Phase 3 trials evaluating safety and effectiveness in hemodialysis patients with moderate-to-severe pruritus. A completed Phase 1 trial also examined the drug's pharmacokinetics in Chinese adult subjects on hemodialysis.

Reported Side Effects

Reports submitted to FDA's adverse event system most commonly describe nervous system and general effects, including dizziness (45 reports), somnolence (40), and falls (35). Other frequently reported terms include death (30), drug ineffectiveness (24), mental status changes (23), confusional state (19), and asthenia (18). These figures reflect raw report counts, not confirmed incidence rates or evidence that the drug caused these events.