The First Potential Kappa Opioid Receptor Agonist: CR845
Cara Therapeutics is developing the first peripherally acting kappa opioid receptor agonist (KORA) called CR845. CR845 is a potent peripheral kappa opioid receptor agonist with high selectivity over other opioid receptors in the body. The degree of kappa receptor selectivity displayed by CR845 ranks as best-in-class compared to all other previously developed compounds for this therapeutic target. Moreover, CR845 displayed no significant affinity for any other non-opioid known receptors.
CR845 exhibits potent analgesic, anti-pruritic (anti-itch) and anti-inflammatory properties in both human and animals. Since CR845 is intrinsically poor at penetrating the blood-brain barrier, it has shown to produce little to no CNS-mediated side effects that one sees with traditional CNS-acting mu opioids like nausea/vomiting, sedation, respiratory depression, abuse, addiction or euphoria.
To date, CR845/difelikefalin has shown anti-pruritic and analgesic properties in 6 different Phase 2 or 3 studies for pruritus (IV formulation for CKD-aP) and acute postoperative pain (IV formulation in laparoscopic hysterectomy, ventral hernia and bunionectomy). Additionally, it has been studied in a human abuse liability (HAL) study which supports the view that CR845/difelikefalin is unlikely to be recreationally abused or lead to physical dependence. In a human abuse liability trial, I.V. CR845/difelikefalin demonstrated statistically significant reductions in “drug liking,” “feeling high,” “overall liking,” and “take drug again” scores in comparison to I.V. pentazocine, a Schedule IV analgesic.
An oral formulation of CR845/difelikefalin is currently being evaluated in a Phase 2 studies in Chronic Kidney Disease associated Pruritus (CKD-aP) Stage 3-5 patients as well as Chronic Liver Disease associated Pruritus (CLDaP) in patients with Primary Biliary Cholangitis (PBC) and patients with Atopic Dermatitis.