Bristol-Myers
Squibb Company (NYSE:BMY) today announced late-breaking data from
the UNITY Trial program investigating a 12-week regimen of its all-oral
daclatasvir (DCV) TRIO regimen – a fixed-dose combination of daclatasvir
with asunaprevir (ASV) and beclabuvir (BCV) – in a broad range of
patients with genotype 1 hepatitis C virus (HCV). The data will be
presented at The Liver Meeting® 2014, the Annual Meeting of
The American Association for the Study of Liver Diseases (AASLD), in
Boston, MA, November 7 – 11. The primary endpoint for both studies was
the percentage of patients who achieved cure, defined as HCV RNA<LLOQ
TD/TND at post-treatment week 12 for treatment-naïve and
treatment-experienced patients.
The UNITY-2 study, which evaluated cirrhotic patients in a 12-week
regimen of the DCV-TRIO, showed sustained virologic response 12 weeks
after treatment (SVR12) among 98% of treatment-naïve and 93% of
treatment-experienced cirrhotic patients with ribavirin (RBV) and 93% of
treatment-naïve and 87% of treatment-experienced cirrhotic patients
without ribavirin.
“Even with the most recent HCV treatment advances, genotype 1 patients
with cirrhosis remain difficult to treat,” said Andrew J. Muir, M.D.,
MHS, Associate Professor of Medicine; Clinical Director,
Gastroenterology & Transplant Hepatology, Duke Gastroenterology.
“Currently, treatment-experienced cirrhotic patients still require a
24-week regimen to achieve high SVR rates. The data from this clinical
trial using the DCV-TRIO regimen showed high cure rates for this
population in a 12-week regimen, and has the potential to aid treatment
adherence and provide a shorter treatment duration to achieve cure.”
Study Design and Results
The Phase 3 UNITY clinical trial program is an ongoing study
investigating 12-week regimens of the DCV-TRIO fixed-dose combination
(daclatasvir 30 mg plus asunaprevir 200 mg plus beclabuvir 75 mg) in
non-cirrhotic and cirrhotic genotype 1 patients.
The open-label UNITY-1 study evaluated a 12-week regimen of the DCV-TRIO
without ribavirin in treatment-naïve and -experienced non-cirrhotic
patients. Non-cirrhotic treatment-naïve patients (n=312) and
treatment-experienced patients (n=103) received the DCV-TRIO fixed-dose
combination in one pill twice daily for 12 weeks, with 24 weeks of
follow-up. The majority of the patients (73%) were genotype 1a, and 91%
of all patients achieved SVR12. 92% of treatment-naive patients and 89%
of treatment-experienced patients achieved cure, without the use of
ribavirin.
In the UNITY-2 study, both cirrhotic treatment-naïve and
treatment-experienced patients received the DCV-TRIO fixed-dose
combination, one arm without ribavirin (n=102) and one with ribavirin
(n=100). The study was double-blinded to ribavirin, and the majority of
the patients (74%) were genotype 1a. The study showed 96% of all
patients who received the DCV-TRIO with ribavirin achieved SVR12, and
90% of those who received the DCV-TRIO without ribavirin achieved SVR12.
“The Phase 3 UNITY results for the daclatasvir TRIO fixed-dose
combination are particularly compelling for genotype 1 patients with
cirrhosis, whose treatment is often harder to manage than non-cirrhotic
patients,” said Douglas Manion, M.D., head of Specialty Development,
Bristol-Myers Squibb. “BMS continues to recognize that HCV is an
extremely complicated disease with no ‘one-size-fits-all’ treatment
solution, and the UNITY results are especially promising for serving
patients with cirrhosis, a specific but significant portion of genotype
1 patients.”
In both UNITY-1 and UNITY-2 there were low rates of adverse events (AEs)
leading to discontinuation and of serious adverse events (SAEs) overall.
In UNITY-1 there were 7 SAEs, all considered not related to study
treatment, and 3 AEs leading to treatment discontinuation. The most
common AEs were headache (25.8%) and fatigue (16.6%). In UNITY-2, there
were 3 SAEs related to treatment and 4 AEs leading to discontinuation.
The most common AEs were headache and fatigue (both 19.8%).
Full abstracts for both presentations are available at The Liver Meeting website.
About Hepatitis C
Hepatitis C is a virus that infects the liver and is transmitted through
direct contact with infected blood and blood products. Approximately 170
million people worldwide are infected with hepatitis C, with an
estimated 2.7–3.9 million chronically infected in the United States. 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 20 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, a potent
pan-genotypic NS5A complex inhibitor (in vitro), which continues
to be investigated in multiple treatment regimens and in people with
co-morbidities.
Daklinza (daclatasvir) was recently approved in the EU for use in
combination with other medicinal products across genotypes 1, 2, 3 and 4
for the treatment of chronic hepatitis C virus (HCV) infection in
adults. Daklinza is also approved in Japan in combination
with Sunvepra (asunaprevir), a NS3/4A protease inhibitor.
The Daklinza+Sunvepra Dual Regimen is Japan’s first
all-oral, interferon- and ribavirin-free treatment regimen for patients
with genotype 1 chronic HCV infection, including those with compensated
cirrhosis.
In 2013, Bristol-Myers Squibb’s investigational all-oral DCV-TRIO
regimen (daclatasvir/asunaprevir/beclabuvir) received Breakthrough
Therapy Designation in the U.S., which helped to expedite the start of
the ongoing Phase 3 UNITY program. Study populations include
non-cirrhotic naïve, cirrhotic naïve and previously treated patients. In
addition to UNITY 1 and 2, both the UNITY-3 study among Japanese
treatment-naïve and -experienced genotype 1 patients and UNITY-4, which
studies the DCV-TRIO regimen without ribavirin in cirrhotic and
non-cirrhotic patients in Korea, Russia and Taiwan, are currently
ongoing. The DCV-TRIO regimen is being studied as a
fixed-dose-combination treatment with twice daily dosing.
Additional studies with daclatasvir in combination with sofosbuvir are
being conducted 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 3 ALLY Program.
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.
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 or
asunaprevir or any other compounds mentioned in this release will
receive regulatory approval in the United States, or if approved, that
they will become commercially successful products. 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, 2013, 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.
Copyright Business Wire 2014