Cara Therapeutics, a biopharmaceutical company focused on developing and commercializing new chemical entities designed to alleviate pain and pruritus by selectively targeting peripheral kappa opioid receptors, announced that the FDA has granted Breakthrough Therapy designation to I.V. CR845 for the treatment of moderate-to-severe uremic pruritus (UP) in chronic kidney disease (CKD) patients undergoing hemodialysis.

“The FDA’s decision to grant Breakthrough Therapy designation is recognition of both the significant unmet medical need among CKD patients with UP and the potential of I.V. CR845 to address it,” said Derek Chalmers, Ph.D., D.Sc., president and chief executive officer of Cara Therapeutics. “We have already initiated our phase III program and look forward to working closely with the FDA to bring this potential new treatment option to hemodialysis patients as quickly as possible.”

Breakthrough Therapy designation is granted to expedite the development and review process for new therapies addressing serious or life-threatening conditions, where preliminary clinical evidence indicates that the drug candidate may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. 

This regulatory decision was supported primarily by positive top-line results from Part A of a phase II/III clinical trial of I.V. CR845 in patients with UP. Part A of the trial met its primary endpoint, with a 68 percent reduction in worst itching scores versus placebo after an eight-week treatment period (p<0.0019), and its secondary endpoint, with a 100 percent improvement in quality of life domains versus placebo (p<0.0007). I.V. CR845 was well-tolerated in the trial.

The 52-week phase III study is enrolling up to 240 hemodialysis patients with CKD-associated pruritus who previously completed one of the company’s phase II/III studies (CR845-CLIN2101 Part A or CR845-CLIN2005 Part B). This open-label trial will evaluate the long-term safety of I.V. CR845 at the dose of 0.5mcg/kg, a dose that met both primary and secondary efficacy endpoints (reduction of itch and improved quality of life, respectively) in patients with moderate-to-severe uremic pruritus (UP).

UP is an intractable systemic itch condition that occurs with the greatest frequency and intensity in 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% 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%) report pruritus, with 30 to 40% reporting moderate or severe pruritus. Recent data from the ITCH National Registry Study showed that among those with pruritus, 59% 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.