FDA Approves Treatment for Uremic Pruritis

In August 2021, the FDA approved difelikefalin (Korsuva) for the treatment of moderate to severe pruritis associated with chronic kidney disease (CKD) in adults undergoing hemodialysis.¹ Uremic pruritis is a common problem for patients with CKD, with limited treatment options. Korsuva is the first FDA-approved treatment for this indication. Difelikefalin is a κ-opioid agonist; the exact mechanism of therapeutic effect is unknown.

Efficacy

Two randomized, placebo-controlled trials (KALM-1, NCT03422653; KALM-2, NCT03636269) demonstrated difelikefalin efficacy in adults with moderate to severe pruritis undergoing hemodialysis (n = 851). Participants received intravenous (IV) injections of either placebo or difelikefalin 0.5 mg/kg of dry body weight at the end of each hemodialysis session 3 times weekly for 12 weeks. Those using medications to treat itch prior to the study were allowed to continue treatment with these medications during the trials.

Prior to randomization, participants kept daily records for 7 days to establish the baseline presence and itch intensity. Mean baseline scores were 7.1 and 7.2 in KALM-1 and KALM-2, respectively. Baseline scores were compared with itch intensity scores assessed at week 12 of therapy. Primary end point was the proportion of patients who achieved a 4-point reduction in itch score at week 12.

In KALM-1, 40% of participants vs 21% in the placebo group met the primary end point (a 19% between-group difference; 95% CI, 9%-28%). In KALM-2, 37% of participants (vs 26% placebo) met the end point for a 12% between-group difference (95% CI, 3%-20%).

Safety

Major adverse events (AEs) across both trials included diarrhea (9%), dizziness (6.8%), nausea (6.6%), gait disturbances inclusive of falls (6.6%), hyperkalemia (4.7%), headache (4.5%), somnolence (4.2%), and mental status changes inclusive of confusional state (3.3%). These AEs occurred at higher rates in the difelikefalin group vs placebo.

In the treatment group, dizziness and somnolence were generally transient and occurred within the first 3 weeks of therapy. Somnolence was more common in older adults (age 65 and older; 7.0% vs 2.8%, respectively).

Some patients in the treatment group discontinued therapy due to gait disturbances, dizziness, and mental status changes. Concomitant administration of opioids, antihistamines, or centrally acting depressant drugs may increase AEs. Difelikefalin is not recommended for use in patients undergoing peritoneal dialysis or in patients with severe hepatic impairment.

Drug Administration

Korsuva is supplied as a clear colorless solution in a single-dose vial; vials should be stored at room temperature. Recommended dose is 0.5 μg/kg of dry body weight/dose. Bolus injection must be administered within 60 minutes of syringe preparation, administered by IV injection into the venous line of the dialysis circuit at the conclusion of each hemodialysis treatment. Administration of the medication during a dialysis session will result in the removal of the drug by the dialyzer membrane. Any unused medication remaining in the vial after a dose has been prepared should be discarded.

Kathryn Wheeler, PharmD, BCPS, is the associate dean of academic affairs and an associate clinical professor of pharmacy practice in the Department of Pharmacy Practice at the University of Connecticut School of Pharmacy

Reference

1. Korsuva. Prescribing information. Vifor Pharma, Cara Therapeutics; 2022. Accessed March 10, 2022. www.accessdata.fda.gov/drugsatfda_docs/label/2021/214916s000lbl.pdf