An evaluation of difelikefalin as a treatment option for moderate-to-severe pruritus in end stage renal disease

ABSTRACT

Introduction: Chronic kidney disease-associated pruritus (CKD-aP), or uremic pruritus, is a severely distressing condition that occurs in greater than 60% of patients undergoing dialysis. However, there are currently no FDA approved treatments for CKD-aP in the United States or Europe. Difelikefalin (DFK) is a kappa opioid receptor agonist with limited central nervous system (CNS) penetration that aims to fill this void by effectively and safely reducing itch in these patients.

Areas covered: Through a review of the current literature (using PubMed and Google Scholar keyword searches of difelikefalin, CR845, pruritus, itch, opioids, hemodialysis, chronic kidney disease, uremic pruritus), the authors review DFK’s mechanism of action and use published clinical trial data to evaluate its effectiveness in treating CKD-aP both individually and comparatively to other treatment alternatives.

Expert opinion: DFK’s IV formulation seems to provide safe, rapid-acting and effective itch reduction in hemodialysis patients without many of the negative mu opioid receptor (MOR)- or CNS- related side effects or drug-drug interactions of other currently available opioids. Its administration through IV bolus immediately after dialysis sessions at dialysis centers also increases availability to and ease of drug scheduling for this target population.

KEYWORDS:

• Chronic kidney disease associated pruritus
• CR845
• Difelikefalin
• end stage renal disease
• hemodialysis associated pruritus
• itch
• kappa opioid agonist
• peripherally restricted kappa opioid agonist
• pruritus
• uremic pruritus

Declaration of interest

G Yosipovitch is a consultant for Trevi Therapeutics and an investigator for Cara Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One referee has given lectures and participated on advisory boards for Vifor Fresenius Medical Care Renal Pharma. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.