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Daclatasvir Plus Asunaprevir Cures Most Genotype 1b Chinese Hepatitis C Patients

An interferon- and ribavirin-free dual combination of Bristol-Myers Squibb's hepatitis C virus (HCV) NS5A inhibitor daclatasvir (Daklinza) and HCV protease inhibitor asunaprevir (Sunvepra) produced sustained response in more than 90% of genotype 1b chronic hepatitis C patients in China, researchers reported at the 25th Conference or the Asian Pacific Association for the Study of the Liver this week in Tokyo. 

HCV subtype 1b, which is common in parts of Asia, is considered easier to treat than subtype 1a, as it less likely to develop drug resistance.

Below is an edited excerpt from a Bristol-Myers Squibb press release describing the study and its findings in more detail.

Data Presented at APASL from First Completed Phase 3 Trial of All-oral Chronic Hepatitis C Regimen in Chinese Patient Population Shows Daclatasvir and Asunaprevir DUAL Therapy Demonstrated High Cure Rates Among HCV Genotype 1b Patients

Princeton, N.J. -- February 22, 2016 -- Bristol-Myers Squibb Company (NYSE:BMY) today announced data from the first completed all-oral chronic hepatitis C (HCV) regimen Phase 3 trial that includes a Chinese patient population. The results of the registrational trial, which studied daclatasvir in combination with asunaprevir for 24 weeks in Asian (non-Japanese) patients with genotype 1b HCV, were presented today at the Asian Pacific Association for the Study of the Liver Conference (APASL) in Tokyo.Genotype 1b is particularly prevalent in China, where interferon/ribavirin combination regimens are still the current standard of care.

The primary endpoint of the study was sustained virologic response at post-treatment week 24 (SVR24). In the study, 91% of patients from China achieved SVR24, which rose to 98% of patients without NS5A resistance-associated variants (RAVs) at baseline. SVR24 results were similarly high across all subgroups with genotype 1b HCV, including those with cirrhosis (90%), and patients from Korea (94%) and Taiwan (87%).

SVR24 rates were also higher in all patients without baseline NS5A RAVs (n=137/139 [99%]), regardless of the presence (98%) or absence (99%) of cirrhosis, and lower in patients with baseline NS5A RAVs (n=8/19 [42%]).Baseline NS5A RAVs were present in 12% of patients.HCV NS5A RAVs exist naturally (albeit in lower prevalence vs wildtype) and can emerge after virologic response failure. Screening for the presence of specific NS5A mutations can help physicians determine the best patients for treatment by identifying those most likely to achieve cure with an NS5A-containing regimen.

In the trial presented today, across all patient cohorts, all serious adverse events (SAEs) (n=5/159 [3%]), grade 4 laboratory abnormalities (n=3/159 [1.9%]) and deaths (n=1/159 [1%]) that occurred on treatment were unrelated to the study drugs. Two patients discontinued due to adverse events (AEs). The most common AEs (> 5% of patients) were decrease in platelets (9%), upper respiratory tract infection (8%), ALT increase (7%), ANC decrease (7%), monocyte decrease (6%), white blood cell decrease (6%), thrombocytopenia (6%), and pruritus (6%).

"These results signal that the daclatasvir and asunaprevir regimen could provide a highly effective all-oral, interferon- and ribavirin-free treatment for many Chinese HCV patients with genotype 1b infection," said Dr. Lai Wei, Professor of Hepatology and Medicine and Director, Peking University Hepatology Institute, Chief, Department of Hepatology, Peking University People’s Hospital. "This is an important finding because the burden of HCV in China is extremely high, and newer direct-acting antivirals have yet to be introduced for any patients."

The daclatasvir and asunaprevir regimen already is approved by regulatory authorities in several countries across the Asia Pacific region, including Japan, Korea and Taiwan, as well as in some countries in Latin America and Eastern Europe. At APASL, Bristol-Myers Squibb is also presenting other data for the daclatasvir and asunaprevir regimen in Asian populations, including integrated safety, pooled resistance and pooled exposure data.

"So much progress has been made globally in the fight against chronic hepatitis C, but the battle against the disease is not over," said Douglas Manion, MD, head of Specialty Development, Bristol-Myers Squibb. "At Bristol-Myers Squibb, we continue to seek out areas and patient populations that remain in need of new treatment solutions, such as China, where at last count 13 million people are estimated to be living with the disease."

Study Design

The Phase 3, open-label study evaluated daclatasvir and asunaprevir in interferon- ineligible and/or intolerant non-Japanese Asian patients with chronic HCV genotype 1b infection. Patients received daclatasvir 60 mg (tablet) once daily plus asunaprevir 100 mg (soft capsule) twice daily for 24 weeks. The primary endpoint was sustained virologic response at post-treatment week 24 (SVR24). The study treated 159 patients overall, 80% from mainland China, 11% from Korea and 9% from Taiwan, including patients with cirrhosis (33%), IL28B nonCC genotypes (40%), and aged >70 years (4%).

About Hepatitis in China

HCV represents a significant public health burden in China and is now the fourth most commonly reported infectious disease countrywide. An estimated 13 million Chinese are currently living with HCV, and genotype 1b, one of seven major genotypes of the virus, is the most common, representing 57% of the total infected population in China.

About Daclatasvir

In many countries, daclatasvir, marketed as Daklinza, is approved as part of a regimen with sofosbuvir. Daklinza is approved by the U.S. Food and Drug Administration (FDA) for use with sofosbuvir, with or without ribavirin, for the treatment of patients with HCV genotype 1 or genotype 3 infection. SVR rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving Daklinza in combination with sofosbuvir for 12 weeks. When Daklinza is used in combination with other agents, the contraindications applicable to those agents are applicable to the combination regimen. Daklinza is contraindicated in combination with drugs that strongly induce CYP3A and P-glycoprotein transporter, and, thus, may lead to lower exposure and loss of efficacy of Daklinza.Please see full Important Safety Information below for more details.

About Bristol-Myers Squibb in HCV

Bristol-Myers Squibb is focused on helping to eradicate hepatitis C around the world, with a primary emphasis on difficult-to-treat patients, including those millions in countries where population-based HCV solutions remain a high unmet need.      

In July 2014, Japan became the first country in the world to approve the use of a daclatasvir-based regimen for the treatment of chronic hepatitis C. Since then, daclatasvir-based regimens have been approved in more than 50 countries across Europe, Central and South America, the Middle East and the Asia-Pacific region.

U.S. Indication and Important Safety Information - DAKLINZA™ (daclatasvir)

[See full press release]

Please click here for the Daklinza full prescribing information.

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 about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, and YouTube.

2/23/16

Source

Bristol-Myers Squibb. Data Presented at APASL from First Completed Phase 3 Trial of All-oral Chronic Hepatitis C Regimen in Chinese Patient Population Shows Daclatasvir and Asunaprevir DUAL Therapy Demonstrated High Cure Rates Among HCV Genotype 1b Patients. Press release. February 22, 2016.