Results of Japanese Phase III Clinical Study of KORSUVA® IV Injection for Pruritus in Patients undergoing Hemodialysis Published in NEJM Evidence

Kissei Pharmaceutical Co., Ltd.
Maruishi Pharmaceutical Co., Ltd.

Kissei Pharmaceutical Co., Ltd. (Head Office: Matsumoto, Nagano, Japan; Chairman and CEO: Mutsuo Kanzawa; "Kissei") and Maruishi Pharmaceutical Co., Ltd. (Head Office: Tsurumi, Osaka, Representative Director and President: Katsuhito Inoue; "Maruishi") today announced that the results of the double-blind period of the phase III clinical study of KORSUVA® IV Injection (generic name: difelikefalin acetate, development code: MR13A9 "KORSUVA®"), which obtained manufacturing and marketing authorization in Japan on September 25, 2023¹ for the treatment of pruritus in patients undergoing hemodialysis, were published in NEJM Evidence².

The phase III study (Study Name: MR13A9-5) was a placebo-controlled, double-blind, parallel-group comparison study conducted in 178 hemodialysis patients with pruritus. During the 6-week double-blind period, patients were administered KORSUVA® or placebo. The change from baseline in mean itch Numerical Rating Scale (NRS) score at week 4, which was the primary endpoint, in the placebo and KORSUVA® groups was -1.09 and -2.06, respectively. The difference between the groups demonstrated that the KORSUVA® group was superior to the placebo group (P<0.001). Furthermore, the incidence of treatment-related adverse events was 15% for the KORSUVA® group and 3% for the placebo group.

KORSUVA® is a kappa opioid receptor agonist originated and developed by Cara Therapeutics, Inc. (Head Office: USA, President and CEO：Christopher Posner). The product will be manufactured by Maruishi and marketed by Kissei in Japan.

Kissei and Maruishi strive to expand treatment options for uremic pruritus to contribute to improving the QOL of patients undergoing hemodialysis.

1. News Release: September 25, 2023.
　KORSUVA^® IV Injection Syringe 17.5μg, 25.0μg and 35.0μg Granted Marketing Authorization Approval in Japan for Treatment of Pruritus in Patients Undergoing Hemodialysis.

2. Ichiei Narita, et al. Difelikefalin for Hemodialysis Patients with Pruritus in Japan.
　NEJM Evidence. Published October 17, 2023. DOI: 10.1056/EVIDoa2300094
　URL https://evidence.nejm.org/doi/full/10.1056/EVIDoa2300094

《 Reference 》

About uremic pruritus in dialysis patients
Uremic pruritus is a common itching condition in spite of the absence of obvious skin lesion, which occurs in many patients with end-stage renal disease undergoing hemodialysis.
It is reported that long-lasting and intense distressing itching in these patients make their QOL very low and have negative impacts on psychological and physical health such as poor sleep quality, depression, and an increased risk of death.
It is considered that endogenous opioids are related to pruritus as one of the expression mechanisms of pruritus in dialysis patients. Difelikefalin acetate selectively activates kappa opioid receptor which is one of the subtypes of opioid receptors, and is indicated to suppress pruritus.

About KORSUVA® IV Injection Syringe
KORSUVA® is indicated for the treatment of pruritus in hemodialysis patients (for use only when conventional treatments are not sufficiently effective). It is provided as a pre-filled syringe formulation to facilitate convenience in the medical environment.
In April 2013, Maruishi acquired certain rights from Cara, and since March 2017, Maruishi and Kissei have been jointly developing KORSUVA® for the indication of uremic pruritus in Japan. The manufacturing and marketing approval in Japan was obtained on September 25, 2023.

About NRS (Numerical Rating Scale) score for itch
The NRS score for itch is a score that evaluates with an integer from 0 to 10 where "no itch" is 0 and "the worst itch" is 10 for the most intense itching felt in the day.

About Kissei Pharmaceutical Co., Ltd.
Kissei is a Japanese pharmaceutical company based on the management philosophy "contributing to society through high-quality, innovative pharmaceutical products" and "serving society through our employees." As a strong R&D-oriented corporation, it concentrates on providing innovative pharmaceuticals to patients worldwide in the focus fields of urology, nephrology/dialysis, gynecology and rare/intractable diseases.
For more details about Kissei Pharmaceutical Co., Ltd., please visit https://www.kissei.co.jp/.

About Maruishi Pharmaceutical Co., Ltd.
Maruishi is a specialty pharma that has a strong presence in the perioperative and infection control area, and is known as a leading producer of Japanese Pharmacopoeia drugs. Making use of the technology, knowledge, and know-how that have been cultivated over 130 years of history, Maruishi continues to contribute to the healthcare and improvement of QOL of the patients.
For more details about Maruishi Pharmaceutical Co., Ltd., please visit https://www.maruishi-pharm.co.jp/.

About Cara Therapeutics, Inc.
Cara Therapeutics (Nasdaq: CARA) is a commercial-stage biopharmaceutical company leading a new treatment paradigm to improve the lives of patients suffering from pruritus.
For more information, visit https://www.caratherapeutics.com and follow the company on X(Twitter), LinkedIn and Instagram.