Cara Therapeutics Announces Difelikefalin Injection NDA Has Been Submitted in Japan

Cara Therapeutics, Inc. recently announced its licensing partner Maruishi Pharmaceutical Co., Ltd. submitted a New Drug Application (NDA) in Japan for approval of difelikefalin for the treatment of pruritus in hemodialysis patients.

“The NDA submission represents important progress toward bringing difelikefalin injection to hemodialysis patients suffering from pruritus in Japan,” said Christopher Posner, President and Chief Executive Officer of Cara Therapeutics. “In collaboration with our partners, we look forward to making difelikefalin injection available to healthcare providers and hemodialysis patients around the world who need a treatment option to relieve the burden of chronic kidney disease-associated pruritus.”

The NDA includes positive results of a Phase 3 study in Japan, jointly conducted by Maruishi and its sublicensee Kissei Pharmaceutical Co., Ltd., in which 178 patients were administered difelikefalin or placebo for 6 weeks followed by an open-label extension period of difelikefalin administration for 52 weeks. The primary endpoint, change in itch Numerical Rating Scale score, and the secondary endpoint, change in itching scores of Shiratori severity criteria, were significantly improved from baseline compared to the placebo group. Difelikefalin was well-tolerated.

KORSUVA (difelikefalin) injection is approved by the US FDA for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. Cara’s US commercial partner CSL Vifor has launched KORSUVA injection in the US. In addition, KORSUVA is approved by Health Canada and the Health Sciences Authority in Singapore. Under the brand name Kapruvia, it is approved by the European Medicines Agency, the UK Medicines and Healthcare products Regulatory Agency, and the Swiss Agency for Therapeutic Products for the treatment of pruritus associated with chronic kidney disease in hemodialysis patients.

In April 2013, the companies entered into a license agreement under which Cara granted Maruishi an exclusive license to develop, manufacture, and commercialize drug products containing difelikefalin for acute pain and/or uremic pruritus in Japan. Maruishi has the right to grant sub-licenses in Japan, which entitles Cara to receive sub-license fees, net of prior payments made by Maruishi to Cara.

Under the terms of the agreement, Cara is eligible to receive milestone payments upon the achievement of defined clinical and regulatory events as well as tiered, double-digit royalties with respect to any sales of the licensed product sold in Japan by Maruishi, if any, and share in any sub-license fees.

KORSUVA is a kappa opioid receptor agonist developed in Cara laboratories and indicated for the treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD-aP) in adults undergoing hemodialysis (HD). KORSUVA Injection is not a federally controlled substance.

CKD-associated pruritus is an intractable systemic itch condition that occurs with high frequency and intensity in patients with chronic kidney disease undergoing dialysis. Pruritus has also been reported in patients with stage III-V CKD who are not on dialysis. The majority of dialysis patients (approximately 60 to 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, approximately 59% 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 antipruritic treatments, such as antihistamines and corticosteroids, 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. CKD-associated pruritus is also an independent predictor of mortality and the risk for hospitalization among hemodialysis patients.

Cara Therapeutics is a commercial-stage biopharmaceutical company leading a new treatment paradigm to improve the lives of patients suffering from pruritus. The company’s novel KORSUVA (difelikefalin) injection is the first and only FDA-approved treatment for moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. The company is developing an oral formulation of difelikefalin and has initiated Phase 3 programs for the treatment of pruritus in patients with non-dialysis dependent advanced chronic kidney disease and atopic dermatitis. The company has completed a Phase 2 proof-of-concept trial of oral difelikefalin for the treatment of moderate-to-severe pruritus in patients with notalgia paresthetica. A Phase 2 proof-of-concept trial in primary biliary cholangitis patients with moderate-to-severe pruritus is ongoing. For more information, visit www.CaraTherapeutics.com.