Daklinza Label Expansion Includes Patients with HCV Genotype 1

The FDA recently granted approval to a label expansion for daclatasvir (Daklinza) to include hepatitis C (HCV) genotype 1 and revised dosage recommendations for genotype 3.

The label will now include patients with HCV genotypes 1 and 3 co-infected with HIV-1, genotype 1 and 3 patients post-transplant, genotype 1 patients with compensated (Child-Pugh A) cirrhosis and decompensated (Child-Pugh B or C) cirrhosis; and genotype 3 patients with Child-Pugh B or C cirrhosis.

HCV patients with genotype 1 or 3 will use Daklinza with either sofosbuvir (Sovaldi) or with or without ribavirin.

It’s recommended that patients with cirrhosis and HCV genotype 1a should be screened for NS5A polymorphisms at amino acid positions M28, Q30, L31, and Y93.

Daklinza is taken once a day orally with or without food at a recommended dosage of 60 mg.

The starting dose for patients with genotype 1 or 3, with Child-Pugh B or C cirrhosis, or post-transplantation is 600 mg daily. As tolerated, it can increase up to 1000-mg per day. The starting dose for ribavirin can be adjusted based on hemoglobin and creatinine clearance.

The dosage for ribavirin is based on a person’s weight. Genotype 3 patients with Child-Pugh A who weigh less than 75 kg have a dosage of 1000 mg, while patients who weigh at least 75 kg takes 1200 mg divided into 2 doses, and taken with food.

During 3 clinical trials, researchers looked at 2400 people with chronic HCV who were treated with a combination of the recommended dose of Daklinza and other anti-HCV drugs. There were 679 patients who received a regimen of Daklinza and Sovaldi.

During the ALLY-2 clinical trial, 153 patients enrolled were treatment-naïve or treatment experienced and have HCV or HIV-1. These patients were treated for 12 weeks with a combination of 60 mg of Daklinza daily (the dose was adjusted for concomitant antiretroviral use) and Sovaldi.

With a frequency of 10% or greater, the most common adverse reaction to the therapy was fatigue. There were no patients who stopped therapy for adverse effects and most reactions were mild to moderate in severity.

The ALLY-1 trial used 113 patients with chronic HCV, as well as 60 patients with Child-Pugh A, B, or C cirrhosis, and 53 patients with recurrence of HCV after a liver transplantation. These patients had a treatment regimen that consisted of 60 mg daily of Daklinza in combination with Sovaldi and ribavirin for 12 weeks.

Researchers found that out of the 113 patients with an adverse reaction frequency of 10% or greater, the most common effects were headache, fatigue, nausea, and anemia. There were 15 patients (13%) who discontinued Daklinza for adverse reactions, 13 patients (12%) who discontinued ribavirin, and 2 patients (2%) who discontinued all 3 of the drugs. They also saw that 4 subjects with cirrhosis underwent a liver transplantation during treatment.