PRINCETON, N.J.--(
BUSINESS WIRE)--
Bristol-Myers
Squibb Company (NYSE:BMY) today announced results from ALLY-2, a
Phase III clinical trial evaluating the investigational once-daily
combination of daclatasvir and sofosbuvir for the treatment of patients
with chronic hepatitis C virus (HCV) coinfected with HIV – a patient
population that historically has been challenging to treat in large part
due to potential drug-drug interactions between the therapy regimens
used to treat each infection.
“The results of ALLY-2 signal that nearly all HIV-HCV coinfected
patients in the study could be cured of hepatitis C with a 12-week
regimen on daclatasvir and sofosbuvir,” said David Wyles, M.D., ALLY-2
Lead Investigator and Associate Professor of Medicine in the Department
of Medicine, Division of Infectious Diseases at the University of
California San Diego. “The trial demonstrated the dosing flexibility
afforded by the daclatasvir-sofosbuvir regimen did not require
alteration of HIV medications because of potential drug-drug
interactions. This is a paramount consideration for clinicians treating
this patient population.”
Among ALLY-2 patients treated for 12 weeks (treatment-naïve and
-experienced), 97% (n=149/153) achieved cure (sustained virologic
response 12 weeks after treatment; SVR12). The study met the primary
endpoint, with 96% (n=80/83) of treatment-naïve genotype 1 patients
achieving SVR12. Treatment with daclatasvir in combination with
sofosbuvir in this study showed high SVR rates, with no discontinuations
due to adverse events, and no serious adverse events related to study
medications throughout the treatment phase.
“While substantial strides have been made in the battle against
hepatitis C, a significant number of patients with complicated disease
and treatment histories need additional treatment options to help them
achieve hepatitis C cure,” said Douglas Manion, M.D., head of Specialty
Development, Bristol-Myers Squibb. “The ALLY-2 results show that
daclatasvir paired with sofosbuvir produced high cure rates in this
trial regardless of the coinfected patients’ HCV genotype.”
According to the Centers for Disease Control and Prevention (CDC), about
one quarter of HIV-infected persons in the United States - approximately
300,000 people - are also infected with hepatitis C, and HCV infection
progresses more rapidly to liver damage in people living with HIV.
In ALLY-2, high SVR rates occurred among all patients treated for 12
weeks, regardless of prior treatment experience, HCV genotype, cirrhosis
status, concurrent combination antiretroviral therapy regimen, or race.
African-American patients comprised 34% of study participants; in this
patient demographic, SVR12 rates were 98% (n=49/50). ALLY-2 also
included an 8-week arm; 38 of 50 treatment-naïve patients with HCV
achieved SVR12. However, study investigators concluded that further
studies are needed to assess the potential of shorter-duration, all-oral
treatment regimens.
Additional safety data demonstrated a low rate of Grade 3/4 lab
abnormalities in the study: INR (1%), AST (0.5%), Tbili (4%), Lipase
(3%).
About ALLY-2: Study Design
This Phase III open-label clinical trial randomized 151 treatment-naïve
and 52 treatment-experienced HCV (genotypes 1-4) patients coinfected
with HIV-1 on a broad range of antiretroviral regimens, into 3 cohorts.
Among treatment-naïve patients, one cohort received daclatasvir 30, 60,
or 90 mg (dose adjusted for concomitant antiretroviral therapy) plus
sofosbuvir 400 mg once daily for 12 weeks, and another received the same
dosage and combination for 8 weeks.
The treatment-experienced cohort also received daclatasvir 30, 60, or 90
mg plus sofosbuvir 400 mg once daily for 12 weeks. Daclatasvir was
dose-adjusted to accommodate concomitant antiretrovirals: 30 mg with
ritonavir-boosted PIs, 90 mg with NNRTIs except rilpivirine. All cohorts
had follow-up through post-treatment week 24. The primary endpoint was
the SVR12 rate among genotype 1 treatment-naïve patients after 12 weeks
of treatment. Patients with cirrhosis were permitted.