- Results of the HALLMARK-Dual study include data among
genotype 1b cirrhotic and non-cirrhotic, treatment-naive,
non-responder, and peginterferon/ribavirin ineligible and
intolerant patients
- Study reinforces the potential of daclatasvir-based regimens
to treat HCV patients with high unmet needs
MONTREAL,
April 10, 2014 /CNW/ - Phase III
results from the global HALLMARK-Dual study investigating the
all-oral, interferon- and ribavirin-free regimen of daclatasvir
(DCV), a NS5A inhibitor, and asunaprevir (ASV), a NS3 inhibitor,
among genotype 1b hepatitis C virus (HCV) infected patients were
presented this week at the 49th annual meeting of the European
Association for the Study of the Liver (EASL) The
International Liver CongressTM, in London. Results showed that the 24-week
regimen achieved an overall sustained virologic response (a
functional cure) 12 weeks after the end of treatment
(SVR12) among treatment-naïve (90%),
peginterferon/ribavirin non-responder (82%), and
peginterferon/ribavirin ineligible/intolerant (82%) patients,
including cirrhotic and non-cirrhotic patients (84% and 85%). In
the study the DCV+ASV regimen was generally well tolerated.
"The HALLMARK-Dual study results are very
encouraging for persons with hepatitis C, particularly those with
advanced liver disease," said Dr. Alnoor
Ramji, Clinical Associate Professor of Medicine in the
Division of Gastroenterology at the University
of British Columbia. "While research in this area is
advancing rapidly, there is a high medical need for these potent
treatment regimens that are effective in a broad range of
patients. Ultimately what we want to see is an increased
virologic eradication rates for HCV. The results of this
daclatasvir-based study point in that direction."
These data were part of the company's recent DCV
and ASV NDA submissions to the U.S. FDA, and helped support the
validated marketing authorization application to the European
Medicines Agency for the use of DCV in combination with other
agents for the treatment of adults with HCV with compensated liver
disease, including genotypes 1, 2, 3, and 4. These data are
comparable to a similar Phase III study of this regimen in Japanese
patients, which led to the submission of a New Drug Application
with Japan's Pharmaceutical and
Medical Devices Agency.
Globally, there are 170 million people infected
with HCV, including over 300,000 in Canada, with genotype 1 being the most
prevalent.
"I was infected with hepatitis C in 1970 as a
result of a blood transfusion. I have survived 43 years with
this disease but thanks to recent treatment advances, I am now
cured," said Joan King, Vice
President of British
Columbia-based HepCBC. "When I talk to other diagnosed
patients we are very hopeful because the cure rates for this
disease are increasing thanks to research like this."
Study Design and Results
This Phase III multinational clinical trial included 116 sites in
18 countries, including countries that have a high prevalence of
GT1b such as Korea and Taiwan. In
the study, treatment-naïve patients (n=205) received DCV 60 mg once
daily plus ASV 100 mg twice daily for 12 weeks, and 102 patients
received matching placebo for 12 weeks. The DCV+ASV treatment-naïve
group continued treatment through week 24; placebo recipients
entered another DCV+ASV study. The
peginterferon/ribavirin-ineligible/intolerant (n=235) and
non-responder patients (n=205) received the same doses of DCV and
ASV for 24 weeks. The primary endpoint was the percentage of
patients with a sustained virologic response at 12 weeks after the
end of treatment(SVR12).
Virologic Response
- 90% of treatment-naïve patients achieved SVR12
- 82% of patients with prior null or partial response to
peginterferon/ribavirin (non-responders) achieved
SVR12
- 82% of peginterferon/ribavirin ineligible/intolerant patients
achieved SVR12
-
- Among peginterferon/ribavirin ineligible/intolerant patients,
SVR12 was achieved by patients with anemia/neutropenia
(91%); depression (80%) and compensated advanced fibrosis/cirrhosis
with thrombocytopenia (73%).
Results among Cirrhotic Patients treated with
DCV+ASV
- At baseline, 33 treatment-naïve, 63 non-responders, and 111
ineligible/intolerant patients had cirrhosis. Cirrhotic patients
made up ~32% of the study population.
- SVR rates were similar in non-cirrhotic (85%) and cirrhotic
(84%) patients.
The regimen used in this Phase III study
resulted in low rates of discontinuation (1-3%) due to adverse
events (AEs). In addition, the rate of serious adverse events
(SAEs) was low (5-7%). Headache was the most common AE in the study
(24-25%). No deaths occurred, and no clinically meaningful
differences were observed in frequencies of SAEs, AEs leading to
discontinuation, or grade 3/4 ALT/AST (liver enzymes) elevations in
patients with or without cirrhosis. Importantly, all grade 3/4
ALT/AST elevations observed were reversible and resolved
off-treatment.
About Hepatitis C
Hepatitis C is a virus that infects the liver and is transmitted
through direct contact with infected blood and blood products. Up
to 90 percent of those infected with hepatitis C will not
spontaneously clear the virus and will become chronically infected.
According to the World Health Organization, up to 20 percent of
people with chronic hepatitis C will develop cirrhosis; of those,
up to 25 percent may progress to liver cancer.
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 (DCV), an investigational NS5A replication
complex inhibitor that has been studied in more than 5,500 patients
as part of multiple direct-acting antiviral (DAA) based combination
therapies. DCV has shown a low drug-drug interaction profile,
supporting its potential use in multiple treatment regimens and in
people with co-morbidities.
Daclatasvir is being investigated in combination
with sofosbuvir in high unmet need patients, such as pre- and
post-transplant patients, HIV/HCV co-infected patients, and
patients with genotype 3, as part of the ongoing Phase III ALLY
Program.
About Bristol-Myers Squibb Canada
Bristol-Myers Squibb Canada is an
indirect wholly-owned subsidiary of Bristol-Myers Squibb Company, 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
www.bmscanada.ca.
SOURCE Bristol-Myers Squibb Canada