Difelikefalin is a peripherally restricted kappa opioid agonist, developed by Cara Therapeutics Inc. that targets the body’s peripheral nervous system. It is being developed as a treatment for chronic kidney disease-associated pruritus (CKD-aP), which is a systemic itch condition that affects patients undergoing haemodialysis and peritoneal dialysis. Vifor Fresenius Medical Care Renal Pharma entered into a development and licensing agreement with Cara Therapeutics to commercialise Difelikefalin injection worldwide (excluding the US, Japan and South Korea).
Moderate-to-severe chronic kidney disease-associated pruritus is associated with poor quality of life, depression, and is an independent predictor of mortality among haemodialysis patients.10
There are currently no approved therapies in Europe or the US for treatment of CKD-aP
Due to the high unmet patient need, the US Food and Drug Administration has granted breakthrough therapy designation to Difelikefalin for the treatment of CKD-aP in haemodialysis patients.
How does Difelikefalin work?
Difelikefalin acts as an analgesic, by activating the K-opioid-receptors in the peripheral nervous system and in the immune system. Therefore, it reduces the transmission of pain signals and reduces the release of prostaglandins, which cause the itching.
Kappa-opioid agonists have been specifically designed to mitigate the drawbacks or side effects typically observed with opiates, such as hallucination or opioid addiction.11
Results from the KALM-2 pivotal phase III trial demonstrated that that Difelikefalin significantly reduce itch intensity, it was generally well-tolerated with a safety profile consistent with that seen in previous trials.