Pooled Analysis Confirms Daclatasvir + Sofosbuvir Safety in Chronic HCV

SAN FRANCISCO, CA—Daclatasvir plus sofosbuvir with or without ribavirin “is a safe and well-tolerated treatment for a broad range of patients with chronic hepatitis C virus (HCV) infection,” a study presented at The Liver Meeting® 2015 has found.

The presence of GT3 infection, HIV/HCV coinfection, advanced cirrhosis, or post-transplant HCV recurrence has minimal impact on safety,” noted Charles S. Landis MD, PhD, of the University of Washington School of Medicine, Seattle, WA.

Dr. Landis and colleagues pooled individual patient data from Phase 2 and 3 studies in which treatment for 8, 12, or 24 weeks with the pangenotypic combination of daclatasvir and sofosbuvir, with or without ribavirin, had achieved high rates (82%–99%) of sustained virologic response (SVR) in numerous HCV-infected populations.

Included were 679 patients with HCV infection who were treatment-naïve and treatment-experienced who also had advanced cirrhosis or post-transplant recurrence (the ALLY-1 trial), HIV/HCV co-infection (ALLY-2), HCV genotype (GT) 3 infection (ALLY-3), and chronic HCV infection (AI444-040).

“Pooled data were analyzed for on-treatment adverse events (AEs), serious AEs, AE-related discontinuations, and Grade 3/4 AEs and lab abnormalities,” Dr. Landis stated. The patients were divided into those who received daclatasvir plus sofosbuvir with and without ribavirin.

The patients were 67% male; 80% were white and 16% black, and median age was 55 years. A total of 18% had cirrhosis, half with hepatic decompensation (Child-Pugh class B and C). Nearly half of the patients (49%) had HCV GT1a infection; the others had GT1b (13%), GT2 (7%), GT3 (30%), GT4 (1%), and GT6 (0.1%).

“Overall, 98% of patients completed treatment,” he noted. The most common AEs of any grade were fatigue, headache, and nausea.

“Serious AEs, grade 3/4 AEs, and AE-related discontinuations were infrequent but more common in patients receiving ribavirin,” the pooled data showed; few AEs were treatment-related. Four deaths occurred after treatment was completed that were unrelated to study drug, two in each of arm.

Among patients with or without compensated cirrhosis, treatment with daclatasvir plus sofosbuvir resulted in comparable safety. In those who had cirrhosis—most with hepatic decompensation—slightly higher rates of serious AEs, anemia, and liver-related lab abnormalities were observed compared with non-cirrhotics. Ribavirin also led to more AEs resulting in treatment discontinuations (8%), compared with <1% among those who did not receive ribavirin.

“There were few safety signals in this diverse population receiving a broad range of concomitant medications, including antiretroviral and immunosuppressive agents,” Dr. Landis concluded.
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