AbbVie submitted a New Drug Application (NDA) to the Japanese Ministry of Health, Labour and Welfare (MHLW) seeking approval for the company's investigational, all-oral, ribavirin (RBV) and interferon (IFN)-free, 12-week, two direct-acting antiviral treatment of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r), dosed once daily. The submission is for the treatment of patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection.
The NDA is supported by the phase 3 GIFT-I study, which met its primary endpoint, achieving a 95 percent (n=106/112) sustained virologic response rate at 12 weeks post-treatment (SVR12) in the sub-group of previously untreated, non-cirrhotic, adult genotype 1b (GT1b)-infected Japanese patients who were eligible for therapy with IFN and had a high viral load (= 100,000 IU/mL). Additionally, two patients without cirrhosis (0.9 per cent) discontinued treatment due to adverse events. GIFT-I included a placebo-controlled arm and studied patients with and without compensated cirrhosis, who were new to therapy or treatment-experienced (with IFN and with or without RBV).
"We are pleased to announce the regulatory submission of our two direct-acting hepatitis C antiviral treatment in Japan, which follows on quickly from recent approvals of our three direct-acting antiviral treatment in the US, Canada and the European Union," says Scott Brun, MD, vice president, pharmaceutical development, AbbVie. "This submission is based on a large phase 3 study in multiple patient types and brings us closer to offering the possibility of cure for patients with chronic genotype 1b hepatitis C infection, the most common form of the disease in the country."
AbbVie studied a two direct-acting antiviral regimen without RBV in Japan due to patient and viral characteristics specific to the Japanese population, including high prevalence of GT1b. In Japan, approximately 1.5 to 2 million people are living with HCV.1 Genotype 1 is the most common HCV genotype in Japan with 60 to 70 percent of patients infected and, of those, about 95 percent are infected with the GT1b sub-type.
GIFT-I (M13-004) is a phase 3, multi-centre study designed to evaluate the efficacy and safety of 12 weeks of treatment with ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in adult Japanese patients (n=363) with chronic genotype 1b hepatitis C virus infection. Patients included those without cirrhosis and with compensated cirrhosis, who were new to therapy (treatment-naïve) or had failed previous treatment with interferon with or without ribavirin (treatment-experienced).
The study consists of two sub-studies. Sub-study one included patients without cirrhosis randomised to OBV/PTV/r or placebo. Sub-study two included patients with compensated cirrhosis, who received open-label treatment with OBV/PTV/r.
Within the primary efficacy patient population, there were no on-treatment virologic failures and 2.8 per cent of patients (n=3/109) experienced relapse.
In patients without cirrhosis, the most commonly reported adverse events in the treatment arm were nasopharyngitis (16.7 per cent OBV/PTV/r vs. 13.2 per cent placebo), headache (8.8 per cent OBV/PTV/r vs. 9.4 per cent placebo), and oedema peripheral (5.1 per cent OBV/PTV/r vs. 0 per cent placebo).
For the treatment of genotype 1 chronic hepatitis C virus (HCV) infection in Japan, AbbVie's investigational two direct-acting antiviral treatment consists of the fixed-dose combination of paritaprevir/ritonavir (150/100 mg) with ombitasvir (25 mg), dosed once daily.
AbbVie's chronic HCV treatment combines two direct-acting antivirals, each with a distinct mechanism of action that targets and inhibits specific HCV proteins of the viral replication process.
AbbVie's HCV clinical development program in Japan focuses on its investigational, two direct-acting antiviral treatment and is designed with the goal of achieving high SVR rates in chronic HCV infected patients, including additional genotypes and patients with compensated cirrhosis.
Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals for HCV protease inhibitors and regimens that include protease inhibitors. Paritaprevir has been developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of hepatitis C.
Ombitasvir/paritaprevir/ritonavir is an investigational product and its safety and efficacy have not been established in Japan.