Bristol-Myers Squibb Company has announced results from ALLY-2, a Phase III clinical trial evaluating the investigational once-daily regimen of daclatasvir and sofosbuvir for the treatment of patients with chronic hepatitis C virus (HCV) co-infected 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 co-infected 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*).1 The study met the primary endpoint, with 96% (n=80/83) of treatment-naïve genotype 1 patients achieving SVR12.1 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.1
"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 co-infected patients' HCV genotype."
According to investigators from the UK Collaborative HIV Cohort (UK CHIC), nearly 9% of HIV-positive individuals in the UK - approximately 9,000 people - are also infected with HCV,3, 4 and HCV infection progresses more rapidly to liver damage in people with concurrent HIV infection.5
In ALLY-2, high SVR 12 rates were observed in the vast majority of the patients treated for 12 weeks, regardless of prior treatment experience, HCV genotype (1-4), cirrhosis status, concurrent combination antiretroviral therapy regimen, or race.1 ALLY-2 also included an 8-week arm; 76% (38 /50) of 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 for Grade 3/4 lab abnormalities in the study: international normalised ratio (1%), Aspartate aminotransferase (0.5%), Total bilirubin (4%), Lipase (3%).1
About ALLY-2: Study Design1
This Phase III open-label clinical trial randomised 151 treatment-naïve and 52 treatment- experienced HCV (genotypes 1-4) patients co-infected with HIV-1 on a broad range of antiretroviral regimens, into three 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 protease inhibitors, 90 mg with Non-Nucleoside Reverse Transcriptase Inhibitors 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.