Vifor Fresenius Medical Care Renal Pharma has licenced ex-US/Japanese/Korean rights to commercialise CR845 (difelikefalin) from Cara Therapeutics for the treatment of chronic kidney disease-associated pruritus (CKD-aP).
Under the terms of the agreement, Cara will receive an upfront payment of US$50m in cash and equity investment of US$20m to acquire Cara common stock. Vifor Pharma did not disclose the amount of potential future milestones and sales royalties. Cara retains development and commercialisation rights for CR845 injection for the treatment of CKD-aP in the US, where the FDA granted breakthrough designation in 2017 for the treatment. Pruritus affects about 20 million people in the US. Cara will solely promote the peripherally acting kappa opioid receptor agonist in all non-FMC clinics in the US. Vifor and Cara will promote CR845 (difelikefalin) to Fresenius Medical Care North America dialysis clinics under a profit-sharing arrangement.
"CR845 injection is a first-in-class, innovative investigational medicine for treating a highly debilitating disease. It is a natural fit to our leading product portfolio in nephrology, and we look forward to making it available to patients who urgently need better therapy," said Stefan Schulze, Vifor Pharma President of the Executive Committee and COO. "Sixty to 70% of dialysis patients experience CKD-aP. Nearly 20% suffer from a very severe form, which is associated with much lower survival. And despite this clear unmet medical need, there is no approved treatment for CKD-aP in Europe or the US. CR845 injection does not penetrate the brain and so bypasses unwanted side-effects like opioid addiction. It has significant potential for setting new standards in providing relief, both from CKD-aP-induced itching and post-operative pain."
CR845 injection is a potent itch and inflammation suppressant without the undesirable side-effects typical of a centrally-acting opioid medicine such as hallucination or opioid addiction. If approved, CR845 injection will be the first medicine for this indication outside of Japan. Vifor Pharma has also secured the first right of negotiation for using CR845 injection to treat post-operative pain outside of the US, Japan and South Korea, for which a Phase-III development programme started in September 2015.
Uremic pruritus (UP) is an intractable systemic itch condition that occurs with the greatest frequency and intensity in chronic kidney disease (CKD) patients under hemodialysis (HD) and peritoneal dialysis; however, pruritus has also been reported in CKD patients who are not yet on dialysis. Aggregate, longitudinal, multi-country studies estimate the weighted prevalence of UP to be approximately 40 percent of patients with end-stage renal disease (ESRD), with approximately 24 percent of patients reporting severe pruritus. Similarly, the majority of dialysis patients (approximately 60-70 percent) report pruritus, with 30 to 40 percent reporting moderate or severe pruritus. Recent data from the ITCH National Registry Study showed that among those with pruritus, 59 percent had experienced symptoms daily or nearly daily for more than a year. Given its association with CKD/ESRD, most afflicted patients will continue to have symptoms for months or years with currently employed anti-pruritic treatments, such as anti-histamines and corticosteroids, which are unable to provide consistent adequate relief. Moderate-to-severe chronic pruritus has repeatedly been shown to directly decrease quality of life, contribute to symptoms that impair quality of life (such as poor sleep quality), and is associated with depression. UP is also an independent predictor of mortality among HD patients, mainly related to increased risk of inflammation and infections.