BMS Submits First All-Oral, Interferon-Free and Ribavirin-Free Treatment Regimen for Regulatory Review in Japan for Patients

  BMS Submits First All-Oral, Interferon-Free and Ribavirin-Free Treatment
  Regimen for Regulatory Review in Japan for Patients with Chronic Hepatitis C

  *An overall SVR[24] rate of 84.7% was achieved in Phase III study of
    daclatasvir (DCV) and asunaprevir (ASV) in high unmet need genotype 1b
    patient population
  *DCV+ASV achieved 87.4% SVR[24] rates in interferon-ineligible/intolerant
    patients and 91.9% SVR[24 ]among this population aged 65+, providing
    potential treatment alternative for many in Japan who currently have no
  *In this study, the DCV+ASV regimen had low rates of discontinuation (5%)
    due to adverse events, and low rates of serious adverse events (5.9%)
  *Data presentation will lead AASLD Viral Hepatitis Presidential Plenary
    session on Tuesday, November 5

Business Wire

PRINCETON, N.J. -- November 2, 2013

Bristol-Myers Squibb Company (NYSE: BMY) today announced the submission of a
New Drug Application (NDA) to Japan’s Pharmaceutical and Medical Devices
Agency seeking the world’s first interferon-free and ribavirin-free treatment
regimen for patients with chronic hepatitis C. The submission is based on
results from a Phase III study demonstrating that the 24-week, all-oral,
interferon-free and ribavirin-free regimen of daclatasvir (DCV) and
asunaprevir (ASV) achieved an overall sustained virologic response 24 weeks
after the end of treatment (SVR[24]) of 84.7% in Japanese patients with
chronic hepatitis C (HCV) genotype 1b who were either
interferon-ineligible/intolerant (87.4% SVR[24]) or non-responders (null and
partial) to interferon-based therapies (80.5% SVR[24]).

These Phase III data will lead the Presidential Plenary at the Viral Hepatitis
Session on November 5 during the 64th Annual Meeting of the American
Association for the Study of Liver Diseases (AASLD) in Washington D.C.

Globally, there are 170 million people who are infected with HCV. Of the 1.2
million people living with HCV in Japan, approximately 70 percent of these
patients have genotype 1b, which has one of the lowest response rates to
current treatments. 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
standard for treating HCV.

“With our submission in Japan, we are pleased to be one step closer to
bringing a potential new treatment option to the many people living with HCV
in that country,” said Brian Daniels, MD, senior vice president, Global
Development and Medical Affairs, Research and Development, Bristol-Myers
Squibb. “The all-oral regimen of DCV plus ASV in this study represents the
potential for a significant advance in the treatment of HCV infection in
Japan, particularly when considering that Japanese patients chronically
infected with HCV are often older than in other countries and predominantly
infected with genotype 1b, both factors which impact response to therapy.”

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 varied among patients.
Nasopharyngitis was the most common adverse event in the study (30.2%,

Study Design and Results

In this open-label, parallel group, Phase III study, interferon-
ineligible/intolerant (IN/I) patients (n=135) and interferon/ribavirin
non-responder (NR) patients (n=87) received DCV 60 mg once daily plus ASV 100
mg twice daily for 24 weeks. The primary endpoint was the percentage of
patients with a sustained virologic response at 24 weeks after the end of
treatment (SVR[24]).

Virologic Response

  *High rates of SVR[24] were achieved in the two studied patient populations
    – those IN/I patients with limited therapeutic options (87.4%, 118/135)
    and those NR patients typically associated with low responses to
    interferon-based therapies (80.5%, 70/87).
  *Patients ≥ 65 years of age had SVR[24] rates similar to those in patients
    < 65 years and age did not appear to impact response rates. SVR[24] rates
    for those ≥ 65 years of age were 91.9% (57/62) in the IN/I elderly patient
    population and 85.2% (23/27) in the NR elderly population.
  *There was no clinically significant difference in SVR[24] by traditionally
    important baseline factors including gender, age, baseline HCV RNA,
    cirrhosis, and IL28B genotype.
  *There were low rates of virologic breakthrough and EOT (end of treatment)
    detectable HCV [ ]RNA (17/222 patients (7.7%)), and low rates of relapse
    (17/205 patients (8.3%)).

“The Phase III study results of daclatasvir plus asunaprevir are exciting to
see, especially in this difficult-to-treat patient population. If approved,
this regimen has the potential to offer HCV patients in Japan, who are unable
to achieve SVR with the current interferon-based standard of care, a new
treatment option,” said lead study investigator Kazuaki Chayama of Hiroshima
University, Japan.

On-Treatment Safety

No deaths were reported and the study discontinuation rate was low (12.6%,
28/222). There were low rates of serious adverse events (5.9%, 13/222) and few
adverse events were reported in greater than 10% of patients. The most common
adverse events reported were nasopharyngitis (30.2%, 67/222), increased ALT
(15.8%), increased AST (12.6%), headache (15.8%), diarrhea (9.9%) and pyrexia
(12.2%). A limited number of Grade 3-4 laboratory abnormalities were observed
in greater than 3 percent of patients.

The most common adverse event leading to discontinuation was ALT/AST
elevation, a measure of liver inflammation. Of the 11 patients who
discontinued due to an adverse event, 10 discontinued due to ALT/AST
elevation. Despite early discontinuation, 80% of these patients achieved
SVR[24] and all ALT/AST values returned to normal.

About Bristol-Myers Squibb’s HCV Portfolio

Bristol-Myers Squibb’s hepatitis C pipeline includes compounds with different
mechanisms of action, pursuing both biologics as well as small molecule
direct-acting antivirals. These compounds are being studied as part of
multiple treatment regimens with the goal of increasing SVR rates across
diverse patient types and geographies.

  *Our investigational NS5A replication complex inhibitor daclatasvir (DCV)
    has been extensively studied in thousands of patients to date as a
    foundational agent for multiple direct-acting antiviral-based (DAA)
    combination therapies.DCV has shown antiviral potency and pan-genotypic
    activity across HCV genotypes in vitro. DCV has a drug-drug interaction
    profile that supports its continued study in a variety of HCV combination
  *Asunaprevir (ASV) is an investigational NS3 protease inhibitor for
    hepatitis C which has been studied as a component of DCV-based treatment
  *BMS-791325 is a non-nucleoside inhibitor of the NS5B polymerase, currently
    in Phase II development for hepatitis C as a component of DCV-based
    treatment regimens
  *Lambda is an investigational type III interferon that has the potential to
    offer an alternative to alfa-interferon in patients for whom an
    interferon-based regimen is required or preferred

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through
direct contact with infected blood and blood products. An estimated 170
million people worldwide are infected with hepatitis C, with genotype 1 being
the most prevalent genotype. Up to 90 percent of those infected with hepatitis
C will not clear the virus and will become chronically infected. According to
the World Health Organization, 20 percent of people with chronic hepatitis C
will develop cirrhosis and, of those, up to 25 percent may progress to liver
cancer. In Japan, the hepatitis C virus is the most common cause of chronic
hepatitis and cirrhosis, and approximately 1.2 million people there are living
with the hepatitis C virus.

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
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Bristol-Myers Squibb Forward Looking Statement

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Bristol-Myers Squibb
Carrie Fernandez, 215-859-2605
Julie Ferguson, 312-385-0098
Ranya Dajani, 609-252-5330
Ryan Asay, 609-252-5020
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