KORSUVA

What it is

Korsuva is a solution for injection containing 50 micrograms of difelikefalin (as acetate) per 1 mL vial. Difelikefalin is a selective kappa opioid receptor agonist with low central nervous system penetration. The physicochemical properties of difelikefalin—a hydrophilic, synthetic D-amino acid peptide with high polar surface area and charge at physiological pH—minimise its passive diffusion and active transport across membranes, thus limiting penetration into the central nervous system. Korsuva is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of the haemodialysis treatment during rinse-back or after rinse-back, three times per week.

Approved indications

— Treatment of moderate-to-severe pruritus associated with chronic kidney disease in adult patients on haemodialysis.

Dosing overview

The recommended dose of Korsuva is 0.5 micrograms/kg dry body weight (the target postdialysis weight) by intravenous bolus injection three times per week. The total dose volume (mL) required from the vial should be calculated as 0.01 multiplied by prescription dry body weight (kg), rounded to the nearest tenth (0.1 mL). Dosing recommendations for elderly patients are the same as for adult patients. If a regularly scheduled haemodialysis treatment is missed, Korsuva should be administered at the next haemodialysis treatment at the same dose. No more than 4 doses per week should be administered even if the number of haemodialysis treatments in a week exceeds 4.

Key safety warnings

Hyperkalaemia frequently occurs in chronic kidney disease patients on haemodialysis, and frequent monitoring of potassium levels is recommended. Difelikefalin has not been studied in patients with New York Heart Association class IV heart failure. In the pivotal clinical studies, a small numerical imbalance of cardiac failure and atrial fibrillation events was observed in difelikefalin-treated patients compared to placebo, particularly among patients with a medical history of atrial fibrillation who discontinued or missed their atrial fibrillation treatment, although no causal relationship was established. Difelikefalin is a peripherally acting kappa opioid receptor agonist with restricted access to the central nervous system. The blood-brain barrier integrity is important for minimising difelikefalin uptake into the CNS. Patients with clinically important disruptions to the blood-brain barrier (such as primary brain malignancies, CNS metastases or other inflammatory conditions, active multiple sclerosis, advanced Alzheimer's disease) may be at risk for difelikefalin entry into the CNS. Korsuva should be prescribed with caution in such patients taking into account their individual benefit-risk balance with observation for potential CNS effects. Dizziness and somnolence have occurred in patients taking difelikefalin and may subside over time with continued treatment. Concomitant use of sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of these adverse reactions and should be used with caution during treatment with difelikefalin. Safety results suggested that compared to placebo, the incidence of somnolence was higher in difelikefalin-treated subjects 65 years of age and older (7.0%) than in difelikefalin-treated subjects less than 65 years of age (2.8%). Therefore, the use of difelikefalin in this patient population should take into account individual benefit-risk assessment and be carefully monitored.

Contraindications

Korsuva is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

PBS listing

Korsuva solution for I.V. injection 50 micrograms (as acetate) in 1 mL is listed on the PBS with 4 items, under authority required restriction, with an ex-manufacturer price of A$540.00.

Regulatory history

Korsuva (difelikefalin) was approved by the TGA on 9 November 2022 for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adult patients on haemodialysis, and was subsequently entered onto the Australian Register of Therapeutic Goods (ARTG) on 10 November 2022. This medicinal product is subject to additional monitoring in Australia, which will allow quick identification of new safety information. The PBAC initially recommended not listing the product in March 2023 for chronic kidney disease-associated pruritus in adult patients on haemodialysis. In November 2023, the PBAC recommended listing for moderate-to-severe pruritus associated with CKD in patients undergoing haemodialysis under Section 100 (Highly Specialised Drugs Program), noting it provides significant improvement in efficacy and is cost-effective with a pre-PBAC response price offer, with a risk sharing arrangement appropriate.