Bristol-Myers Squibb has announced that primary endpoints were successfully met in ALLY-1, a Phase III clinical trial evaluating a 12-week regimen of daclatasvir and sofosbuvir once-daily with ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) with either advanced cirrhosis or post-liver transplant recurrence of HCV.
The study’s primary endpoints were reached, with 95% of post-transplant genotype 1 patients and 82% of genotype 1 patients with advanced cirrhosis achieving SVR12. Among all ALLY-1 patients, 94% of those with post-transplant HCV recurrence and 83% of all participants with advanced cirrhosis achieved cure (sustained virologic response 12 weeks after treatment; SVR12).
No dose adjustments to patients’ transplant related drugs needed while they received the daclatasvir-based regimen
“The results of the ALLY-1 trial point to the potential of this investigational daclatasvir-based regimen in a patient population with high unmet needs despite recent advances in hepatitis C treatment,” said Fred Poordad, M.D., ALLY-1 Lead Investigator and Clinical Professor of Medicine, Chief, Hepatology, University of Texas Health Science Center and VP, Academic and Clinical Affairs Texas Liver Institute. “Transplant patients take a variety of immunosuppressive medications to prevent organ rejection; that complicates the treatment of hepatitis C. In ALLY-1, we saw no drug-drug interactions between transplant and hepatitis C therapies and no need to make dose adjustments to patients’ transplant-related drugs while they received the daclatasvir-based regimen that resulted in high SVR12 rates.”
The Child-Pugh scoring system is commonly used to assess the severity and prognosis of chronic liver disease and cirrhosis, and uses an A through C classification (C being the most advanced) to categorise disease progression. Patients with class C cirrhosis are decompensated, often with later-stage conditions such as ascites, hepatic encephalopathy, and abnormal liver function, which can complicate treatment. The ALLY-1 trial included 16 patients with decompensated cirrhosis Child-Pugh class C; nine (56%) achieved SVR12.
Over the course of the study, four advanced cirrhotic patients received a liver transplant during treatment; 3 of 4 extended treatment post-transplant (see study design below), and all 4 achieved SVR12.
In the study, there were no serious adverse events related to study medications throughout the treatment phase. The most common adverse events (≥10%) were headache (15%, 36%), fatigue (18%, 28%), anemia (20%, 19%), diarrhea (8%, 19%), nausea (17%, 6%), and arthralgia (2%, 13%) in the advanced cirrhotic and post-transplant cohorts, respectively. One patient discontinued therapy after 31 days due to headache, but still achieved SVR12. Nine patients in the cirrhosis cohort relapsed post-treatment, and one had detectable HCV RNA at the end of treatment; there were no on-treatment virologic breakthroughs. Three patients (genotypes 1a, 1b, 3) in the post-transplantation cohort relapsed. All 12 patients with relapse are being retreated with daclatasvir and sofosbuvir with ribavirin for 24 weeks.
Phase III ALLY programme demonstrates the versatility of the daclatasvir-based regimen
HCV is the leading indication for liver transplantation worldwide. Without treatment, HCV infection of the new liver after transplant is inevitable, and is associated with rapid progression to cirrhosis and death in up to 30% of patients within 5 years. The ALLY-1 study is the third study to report out of the Phase III ALLY programme, which evaluates daclatasvir in combination with sofosbuvir in multiple high-unmet need patient populations. The ALLY-2 and ALLY-3 studies have previously been presented at the 2015 Conference for Retroviral and Opportunistic Infections and the 2014 American Association for the Study of the Liver’s The Liver Meeting, respectively, and subanalyses from each study with the ribavirin-free regimen of daclatasvir and sofosbuvir were presented as posters during ILC 2015.
“The ALLY-1 trial results build off the ALLY-2 and ALLY-3 studies by demonstrating the versatility of the daclatasvir-based regimen to provide HCV cure in multiple patient populations that have been historically hard to manage, such as HCV genotype 3 patients, HIV/HCV coinfected patients, and patients with decompensated cirrhosis,” said Douglas Manion, M.D., Head of Speciality Development, Bristol-Myers Squibb. “Post-liver transplant and cirrhotic patients represent a still-unmet need and continue to present challenges to currently available regimens.”
