Bristol-Myers
Squibb Company (NYSE:BMY) today announced late-breaking data from
the landmark ALLY Trial investigating a ribavirin-free 12-week regimen
of daclatasvir (DCV) in combination with sofosbuvir (SOF) in genotype 3
hepatitis C (HCV) patients, a patient population that has emerged as one
of the most difficult to treat. The results of the study, which showed
sustained virologic response 12 weeks after treatment (SVR12) in 90% of
treatment-naïve and 86% of treatment-experienced patients, 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.
“Both treatment naïve and treatment experienced patients in the ALLY-3
study achieved high SVR rates. These results are encouraging given that
patients with genotype 3 have emerged as among the hardest to treat,”
said David R. Nelson, M.D., Professor of Medicine, Molecular
Genetics and Microbiology Director, UF Clinical and Translational
Science Institute, and Assistant Vice President of Research for the
University of Florida. “Genotype 3 is associated with a more rapid
progression of disease and remains a challenge to the efficacy of even
newer regimens. The ALLY-3 results demonstrate the possibility of
bringing a cure to genotype 3 patients in an all-oral, 12-week regimen.”
These results build upon the existing body of data on the daclatasvir
and sofosbuvir combination. Data from an open-label, randomized study
of daclatasvir with sofosbuvir in genotypes 1, 2, and 3 demonstrated
that the 24-week regimen of daclatasvir and sofosbuvir (± ribavirin)
achieved SVR12 in 89% of patients with genotype 3. The ALLY study
presented at The Liver Meeting investigates the regimen for 12 weeks,
halving the previous treatment duration. Other ongoing ALLY studies
examine diverse HCV populations across all genotypes: cirrhotic and
post-liver transplant patients, as well as treatment-naïve and
treatment-experienced patients who are co-infected with HIV.
“HCV is a complex disease, and the treatment community needs multiple
options to address the remaining unmet medical needs,” said Douglas
Manion, M.D., head of Specialty Development, Bristol-Myers Squibb.
“Daclatasvir has shown pan-genotypic activity in bench research, a
factor which is becoming increasingly important as we learn more about
the complexity of HCV. Further, daclatasvir’s potential to be combined
with many other agents, including sofosbuvir, is significant in
continuing to develop additional treatment options that may help
patients of all genotypes achieve cure.”
In the ALLY-3 study, the daclatasvir and sofosbuvir combination regimen
was well tolerated, with no deaths, treatment-related serious adverse
events, or discontinuations due to adverse events. The most frequent
side effects (≥5%) were headache (19.7%), fatigue (19.1%), nausea
(11.8%), diarrhea (8.6%), insomnia (5.9%), abdominal pain and arthralgia
(both 5.3%). Additionally, there were 17 (11.2%) treatment failures,
with 16 relapses post-treatment and 1 rebound at the end of treatment.
There were no viral breakthroughs in this ribavirin-free regimen.
About ALLY-3: Study Design
This Phase 3 open-label clinical trial enrolled 152 genotype 3 HCV
patients; 101 treatment-naïve patients and 51 treatment-experienced
patients in 2 cohorts each received daclatasvir 60 mg and sofosbuvir 400
mg once daily for 12 weeks, with 24 weeks of follow-up. The primary
endpoint was SVR12 rates, defined as HCV RNA < LLOQ target detected or
not detected at follow-up week 12 in treatment-naïve and
treatment-experienced patients.
The full abstract for the presentation is 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 Genotype 3
Genotype 3 is estimated to affect 54.3 million people and is the second
most common worldwide behind genotype 1 (83.4 million). It is now
potentially the most difficult-to-treat genotype, and the more
aggressive nature of genotype 3 lies in the damage it causes to the
liver, as it is associated with progressive disease, increased rates of
steatosis and a disproportionately increased risk of hepatocellular
carcinoma.
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.
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 will
receive regulatory approval in the United States, or if approved, that
it will become a commercially successful product. 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