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Interferon-free Daclatasvir + Asunaprevir Approved in Japan for Hepatitis C

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Bristol-Myers Squibb's all-oral dual regimen of daclatasvir (Daklinza) plus asunaprevir (Sunvepra) has been approved for the treatment of chronic hepatitis C in Japan, where most people are infected with HCV genotype 1b, the company announced this week.

Daclatasvir (formerly BMS-790052) is an NS5A inhibitor and asunaprevir (formerly BMS-650032)is a next-generation HCV protease inhibitor. The 2-drug combination has been shown to be highly effective against HCV genotype 1b, curing 87% of patients who were ineligible for or could not tolerate interferon and 81% of prior non-responders in a Phase 3 study in Japan.

Daclatasvir recently received a favorable opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use. The U.S. Food and Drug Administration is currently reviewing daclatasvir plus asunaprevir, which has been designated as a "breakthrough therapy". Daclatasvir and asunaprevir are also being studied with a third drug, the non-nucleoside polymerase inhibitor BMS-791325, for harder-to-treat HCV genotype 1a, demonstrating a cure rate of 90% in a Phase 2b trial.

Below is an edited excerpt from a Bristol-Myers Squibb press release describing the Japanese approval.

Japan Approves First All-Oral, Interferon- and Ribavirin-Free Hepatitis C Treatment, Daklinza (daclatasvir) and Sunvepra (asunaprevir) Dual Regimen

Offers new treatment option for genotype 1 HCV patients in Japan who are interferon-ineligible/intolerant, or did not previously respond to treatment

Japanese HCV patients in urgent need of care now have opportunity for cure, including older patients and those with compensated cirrhosis

Princeton, N.J. -- July 7, 2014 -- Bristol-Myers Squibb Company (NYSE: BMY) announced today that the Japanese Ministry of Health, Labor and Welfare (MHLW) has approved Daklinza (daclatasvir), a potent, pan-genotypic NS5A replication complex inhibitor (in vitro), and Sunvepra (asunaprevir), a NS3/4A protease inhibitor, providing a new treatment that can lead to cure for many patients in Japan who currently have no treatment options. The Daklinza + Sunvepra Dual Rregimen is Japan’s first all-oral, interferon- and ribavirin-free treatment regimen for patients with genotype 1 chronic hepatitis C virus (HCV) infection, including those with compensated cirrhosis. 

"Japan has a unique hepatitis C patient population, many of whom are older and have been unable to take, or respond to, traditional therapies, so we have a real sense of urgency to treat these patients now," said a lead study investigator Kazuaki Chayama of Hiroshima University in Japan. "The approval of the Daklinza + Sunvepra Dual Regimen offers for the first time a treatment option that addresses many of the unmet needs for our HCV patients."

Of the 1.2 million people living with HCV in Japan, approximately 70% have genotype 1b. Further, a significant number of patients with HCV in Japan are over the age of 65, leading to more disease-related complications and a decreased likelihood of tolerating interferon-based therapies, the historical standard of care for treating HCV. 

The approval of Daklinza + Sunveprain Japan reflects our strategic focus on developing a treatment option that meets the needs of the Japanese HCV patient population," said Lamberto Andreotti, chief executive officer, Bristol-Myers Squibb. "This milestone underscores the company’s commitment to delivering innovative medicines to patients with the highest unmet needs, and we believe Daklinza-based regimens will play a significant role in the evolution of HCV treatment for patients in Japan, and globally."

The Daklinza + Sunvepra Dual Regimen

The indications for Daklinza and Sunvepra in Japan are for the improvement of viremia in either of the following patients with chronic hepatitis C genotype 1, or chronic hepatitis C genotype 1 with compensated cirrhosis: (1) patients who are ineligible or intolerant to interferon-based therapy, and (2) patients who have failed to respond to interferon-based therapy. 

The approval is supported by results from a Phase III study demonstrating that the 24-week regimen of Daklinza and Sunvepra achieved overall SVR24 (sustained virologic response 24 weeks after the end of treatment; a functional cure) among 84.7% of Japanese HCV patients with genotype 1b. Among patients 65 years of age or older who were either interferon-ineligible or intolerant, 91.9% achieved SVR24. Further, patients with compensated cirrhosis present at baseline had overall SVR24 rates of 90.9%.

The regimen used in the Phase III study resulted in low rates of discontinuation (5%) due to adverse events (AEs). In addition, the rate of serious adverse events (SAEs) was low (5.9%) and few SAEs were experienced by more than one patient. Nasopharyngitis was the most common AE in the study (30.2%).

Results from the HALLMARK-Dual study, the Phase III multinational clinical trial investigating the Daklinza + Sunvepra Dual Regimen among genotype 1b HCV patients, demonstrated similar results to the Japan registration study and support filings in countries that have a high prevalence of genotype 1b, such as Korea and Taiwan.

About Bristol-Myers Squibb’s HCV Portfolio

Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir, a potent pan-genotypic NS5A complex inhibitor (in vitro), which continues to be investigated in multiple treatment regimens and in people with co-morbidities, and is undergoing regulatory review in the U.S. and Europe.

Daclatasvir is being studied in combination with sofosbuvir in high unmet need patients, such as pre- and post-transplant patients, HIV/HCV coinfected patients, and patients with genotype 3, as part of the ongoing Phase III ALLY Program.

In 2014, the U.S. Food and Drug Administration (FDA) granted Bristol-Myers Squibb’s investigational Daclatasvir + Asunaprevir Dual Regimen Breakthrough Therapy Designation for use as a combination therapy in the treatment of genotype 1b HCV infection.

In 2013, Bristol-Myers Squibb’s investigational all-oral 3DAA Regimen (daclatasvir/asunaprevir/BMS-791325) also received Breakthrough Therapy Designation in the U.S., which helped to expedite the start of the ongoing Phase III UNITY Program. Study populations include non-cirrhotic naïve, cirrhotic naïve and previously treated patients. The daclatasvir 3DAA regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

7/9/14

Source

Bristol-Myers Squibb. Japan Approves First All-Oral, Interferon- and Ribavirin-Free Hepatitis C Treatment, Daklinza (daclatasvir) and Sunvepra (asunaprevir) Dual Regimen. Press release. July 7, 2014.