General Information

Daklinza (daclatasvir) is a NS5A replication complex inhibitor. 

Daklinza is specifically indicated for use with sofosbuvir for the treatment of patients with chronic hepatitis C virus (HCV) genotype 3 infection.

Daklinza is supplied as tablets for oral administration. The recommended dose is 60 mg taken orally once daily with or without food in combination with sofosbuvir. The recommended treatment duration is 12 weeks. Dose modification: reduce dosage to 30 mg once daily with strong CYP3A inhibitors and increase dosage to 90 mg once daily with moderate CYP3A inducers. 

Clinical Results

FDA Approval

The FDA approval of Daklinza was based on ALLY-3 (AI444-218), an open-label trial that included 152 subjects with chronic HCV genotype 3 infection and compensated liver disease who were treatment-naive (n=101) or treatment-experienced (n=51). Subjects received Daklinza 60 mg plus sofosbuvir 400 mg once daily for 12 weeks and were monitored for 24 weeks post treatment. Sustained virologic response (SVR) was the primary endpoint and was defined as HCV RNA below the LLOQ at post-treatment week 12 (SVR12). The Daklinza plus sofosbuvir regimen demonstrated SVR12 in 90% of treatment-naïve and 86% of treatment-experienced chronic HCV genotype 3 patients. SVR12 rates were higher (96%) in genotype 3 patients without cirrhosis, regardless of treatment history. In the more difficult-to-treat patients with cirrhosis, SVR12 rates were reduced (63%). These SVR12 rates were achieved with 12 weeks of therapy without the use of ribavirin.

Side Effects

 Adverse effects associated with the use of Daklinza may include, but are not limited to, the following:

• headache
• fatigue
• nausea
• diarrhea

Daklinza is contraindicated in combination with drugs that strongly induce CYP3A and, thus, may lead to lower exposure and loss of efficacy of Daklinza.

Mechanism of Action

Daklinza (daclatasvir) is an inhibitor of NS5A, a nonstructural protein encoded by HCV. Daclatasvir binds to the N-terminus of NS5A and inhibits both viral RNA replication and virion assembly. Characterization of daclatasvir-resistant viruses, biochemical studies, and computer modeling data indicate that daclatasvir interacts with the N-terminus within Domain 1 of the protein, which may cause structural distortions that interfere with NS5A functions.

Additional Information

For additional information regarding Daklinza or chronic HCV genotype 3, please visit http://www.daklinza.bmscustomerconnect.com/