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FDA Accepts Resubmitted Application for Hepatitis C Drug Daclatasvir

Virologic response achieved in 90% of treatment-naïve patients

The FDA has accepted Bristol-Myers Squibb’s resubmission of the new drug application (NDA) for daclatasvir, an investigational nonstructural protein 5A (NS5A) replication complex inhibitor, for use in combination with sofosbuvir (Sovaldi, Gilead) for the treatment of patients with chronic genotype-3 hepatitis C virus (HCV) infection.

The original NDA was amended to include data from the phase III ALLY-3 trial, which showed high cure rates for the combination, with a sustained virologic response 12 weeks after treatment (SVR12) in 90% of treatment-naïve and 86% of treatment-experienced genotype-3 HCV patients. The SVR12 rate was higher (96%) in non-cirrhotic genotype-3 patients, regardless of treatment history.

Genotype-3 HCV is estimated to affect 54.3 million people worldwide and is the second most common hepatitis C genotype after genotype 1 (83.4 million). 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.

The open-label ALLY-3 trial enrolled 152 genotype-3 HCV patients; 101 treatment-naïve patients and 51 treatment-experienced patients in two cohorts each received daclatasvir 60 mg and sofosbuvir 400 mg once daily for 12 weeks, with 24 weeks of follow-up. The study’s primary endpoint was the SVR12 rate.

The daclatasvir/sofosbuvir combination regimen was well tolerated in this study, with no deaths, treatment-related serious adverse events (AEs), or discontinuations due to AEs. The most frequent AEs included headache (19.7%), fatigue (19.1%), nausea (11.8%), diarrhea (8.6%), insomnia (5.9%), abdominal pain, and arthralgia (both 5.3%). In addition, there were 17 (11.2%) treatment failures, with 16 relapses post-treatment and one rebound at the end of treatment. There were no viral breakthroughs in this ribavirin-free regimen.

HCV is transmitted through direct contact with infected blood and blood products. Approximately 170 million people worldwide are infected with the virus, with an estimated 2.7–3.9 million chronically infected in the U.S. Up to 90% of those infected with HCV will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20% of people with chronic HCV infection will develop cirrhosis; of those individuals, up to 20% may progress to liver cancer.

Source: Bristol-Myers Squibb; March 12, 2015.

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