Difelikefalin (Korsuva)
Overview
A selective kappa-opioid receptor (KOR) agonist peptide that does not cross the blood-brain barrier, providing peripheral analgesia and anti-pruritic effects without central opioid side effects such as euphoria, dysphoria, sedation, or addiction. Difelikefalin activates kappa receptors on peripheral sensory neurons and immune cells to reduce itch signaling and inflammation. Its restricted CNS penetration is a deliberate design feature to avoid abuse potential.
Key Research Findings
FDA-approved in 2021 for moderate-to-severe pruritus associated with chronic kidney disease (CKD-associated pruritus) in adults undergoing hemodialysis. KALM-1 and KALM-2 trials demonstrated significant reduction in itch intensity vs. placebo, with >40% of patients achieving clinically meaningful itch reduction (Fishbane et al., NEJM, 2020). Oral formulation under development for CKD-associated pruritus in non-dialysis patients and pruritus in liver disease.
Intravenous (post-dialysis)
FDA Approved
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