Bristol-Myers Squibb Release: Data Presented At APASL From First Completed Phase 3 Trial Of All-Oral Chronic Hepatitis C Regimen In Chinese Patient Population Showsdaclatasvir And Asunaprevir DUAL Therapy Demonstrated High Cure Rates Among HCV Genotype 1b

PRINCETON, N.J.--(BUSINESS WIRE)--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.

“So much progress has been made globally in the fight against chronic hepatitis C, but the battle against the disease is not over”

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 & 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, M.D., 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)

INDICATIONS

Daklinza™ (daclatasvir) is indicated for use with sofosbuvir, with or without ribavirin, for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1 or genotype 3 infection.

Limitations of Use:

• Sustained virologic response (SVR12) rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving Daklinza in combination with sofosbuvir for 12 weeks.

CONTRAINDICATIONS

• When used in combination with other agents, the contraindications applicable to those agents are applicable to the combination regimen; refer to the respective prescribing information.
• Drugs contraindicated with Daklinza: strong inducers of CYP3A that may lead to loss of efficacy of Daklinza include, but are not limited to:
  -Phenytoin, carbamazepine, rifampin, St. John’s wort (Hypericum perforatum).

WARNINGS AND PRECAUTIONS

• Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: Coadministration of Daklinza and other drugs may result in known or potentially significant drug interactions. Interactions may include the loss of therapeutic effect of Daklinza and possible development of resistance, dosage adjustments for other agents or Daklinza, possible clinically significant adverse events from greater exposure for the other agents or Daklinza.
• Serious Symptomatic Bradycardia When Coadministered with Sofosbuvir and Amiodarone: Post-marketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with sofosbuvir in combination with another direct-acting antiviral, including Daklinza. A fatal cardiac arrest was reported with ledipasvir/sofosbuvir.
  -Coadministration of amiodarone with Daklinza in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no alternative treatment options, patients should undergo cardiac monitoring, as outlined in Section 5.2 of the prescribing information.
  -Patients also taking beta blockers or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone.
  -Bradycardia generally resolved after discontinuation of HCV treatment.

• Risks Associated with Ribavirin Combination Treatment: If ribavirin is used as part of the regimen, the warnings and precautions for ribavirin, particularly the pregnancy avoidance warning, apply. See the ribavirin full prescribing information for complete information.

ADVERSE REACTIONS

• In clinical trials (Ally 2, 3) with the Daklinza and sofosbuvir regimen, the most common adverse reactions (= 5%) were, respectively: headache (8%, 14%), fatigue (15%, 14%), nausea (9%, 8%), diarrhea (7%, 5%).

• In clinical trials (Ally 1) with Daklinza, in combination with sofosbuvir and ribavirin, the most common adverse reactions (= 5%) were, in the cirrhosis cohort and the post-liver transplantation cohort, respectively: headache (12%, 30%), anemia (20%, 19%), fatigue (15%, 17%), nausea (15%, 6%), rash (8%, 2%), diarrhea (3%, 6%), insomnia (3%, 6%), dizziness (0, 6%), somnolence (5%, 0).

DRUG INTERACTIONS

• CYP3A: Daklinza is a substrate. Moderate or strong inducers may decrease plasma levels and effect of Daklinza. Strong inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir) may increase plasma levels of Daklinza.
• P-gp, OATP 1B1 and 1B3, and BCRP: Daklinza is an inhibitor, and may increase exposure to substrates, potentially increasing or prolonging their adverse effect.
• See Sections 4, 7, and 12.3 of the Daklinza Full Prescribing Information for additional established and other potentially significant drug interactions and related dose modification recommendations. Refer to the prescribing information for other agents in the regimen for drug interaction information.

DAKLINZA IN PREGNANCY:

• No adequate human data are available to determine whether or not DAKLINZA poses a risk to pregnancy outcomes. Animal studies of Daklinza at exposure above the recommended human dose have shown maternal and embryofetal toxicity.
• If Daklinza and sofosbuvir are administered with ribavirin, the information for ribavirin with regard to pregnancy testing, contraception, and infertility also applies to this combination regimen. Refer to the ribavirin prescribing information.

NURSING MOTHERS:

• It is not known whether DAKLINZA is present in human milk, affects human milk production, or has effects on the breastfed infant. Daklinza was present in the milk of lactating rats. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for DAKLINZA and any potential adverse effects on the breastfed child from DAKLINZA or from the underlying condition.
• When Daklinza is administered with ribavirin, the nursing mothers’ information for ribavirin also applies to this combination regimen. Refer to the nursing mothers’ information in the ribavirin prescribing information.

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.

Bristol-Myers Squibb Forward Looking Statement

This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that daclatasvir and asunaprevir will be approved for the indication mentioned above. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2015, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.