AbbVie’s MAVIRET (Glecaprevir/Pibrentasvir) Nears EU Approval for 8-Week First-Line Treatment of Genotype 3 Hepatitis C with Compensated Cirrhosis; Already Marketed in China

February 06, 2020 /BIOON/ -- AbbVie recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending a change to the marketing authorization for Maviret (Chinese brand name: Ainuoquan; generic name: glecaprevir/pibrentasvir), a pangenotypic hepatitis C therapy. The recommendation is to shorten the treatment duration from 12 weeks to 8 weeks for treatment-naive patients with genotype 3 (GT 3) chronic hepatitis C (HCV) infection and compensated cirrhosis.

Currently, Maviret is indicated for: (1) an 8-week, pan-genotypic (GT 1-6), once-daily regimen for treatment-naïve HCV patients without cirrhosis; (2) an 8-week, once-daily regimen for treatment-naïve HCV patients with compensated cirrhosis infected with genotypes 1, 2, 4, 5, or 6; (3) in treatment-naïve patients with genotype 3 and compensated cirrhosis, the recommended treatment duration with Maviret is 12 weeks.

Now, the CHMP opinion will be submitted to the European Commission (EC) for review, which is expected to make a final decision within the next few months. If approved by the EU, Maviret will become the only 8-week treatment regimen for treatment-naïve HCV patients with or without compensated cirrhosis, regardless of genotype.

Janet Hammond, M.D., Vice President of the Integrated Medical and Virology Therapeutic Area at AbbVie, stated, “The HCV treatment pathway can be a complex journey for the millions of patients affected by this disease. Today, the CHMP’s positive opinion on Maviret brings us one step closer to our goal of providing an effective 8-week treatment option for the majority of HCV patients, potentially simplifying the treatment process for most HCV patients, regardless of genotype.”

The CHMP’s positive opinion is based on data from the Phase IIIb EXPEDITION-8 study. This study evaluated the efficacy and safety of Maviret in treatment-naïve patients with compensated cirrhosis and hepatitis C virus (HCV) genotypes 1–6 (n=343). The data showed that the 8-week Maviret regimen achieved a virologic cure rate (SVR12, defined as sustained virologic response 12 weeks after completion of therapy) of 97.7% (n=335/343) in patients with genotypes 1–6 and 95.2% (n=60/63) in patients with genotype 3. To date, one case of virologic failure has been reported in these patients, and no patients discontinued treatment due to adverse events. Adverse events reported in the study (incidence >5%) included pruritus (8%), fatigue (9%), headache (8%), and nausea (6%). Six serious adverse events (2%) occurred during the study, none of which were considered related to Maviret. No new safety signals were identified in this study.

Stefan Zeuzem, MD, Director of the Department of Medicine at Goethe University Hospital in Frankfurt, Germany, stated: “Successfully treating patients with hepatitis C virus (HCV) has historically been a challenge, partly due to the long duration of therapy and the need for additional testing to determine the patient’s HCV genotype and stage of fibrosis in order to select the most appropriate treatment regimen. Clinically validated HCV treatment regimens can reduce both treatment duration and diagnostic burden, which may enable providers to treat more patients, minimize losses associated with subsequent care, and ultimately help accelerate the global elimination of this disease.”

Maviret is a pan-genotypic, once-daily, ribavirin-free therapeutic regimen composed of two fixed-dose unique antiviral agents: glecaprevir (G, 100 mg), an NS3/4A protease inhibitor, and pibrentasvir (P, 40 mg), an NS5A inhibitor. Maviret is administered orally once daily as three tablets.

Maviret is approved for the treatment of hepatitis C virus (HCV) infection across all major genotypes (GT1–6) in adolescents (aged 12 to 18 years) and adults. Maviret is an 8-week pangenotypic (GT1–6) regimen indicated for treatment-naïve patients without cirrhosis, as well as for treatment-naïve patients with compensated cirrhosis infected with GT1, 2, 4, 5, or 6. For treatment-naïve patients with compensated cirrhosis and GT3 infection, the recommended duration of Maviret therapy is 12 weeks.

Maviret is also approved for the treatment of patients with special challenges, including those with all major genotypes and compensated cirrhosis, as well as patients with previously limited treatment options, such as those with severe chronic kidney disease (CKD) or genotype 3 (GT3). Maviret is approved for use in patients with CKD at all stages. The drug is contraindicated in patients with severe hepatic impairment (Child-Pugh C) and is not recommended for patients with moderate hepatic impairment (Child-Pugh B).

In China, Maviret (glecaprevir/pibrentasvir) was approved in May 2019 for the treatment of adult patients with hepatitis C virus (HCV) infection of all major genotypes (GT1, 2, 3, 4, 5, and 6) who have no cirrhosis or compensated cirrhosis. With an 8-week cure rate for hepatitis C, Maviret was included in the second batch of urgently needed overseas new drugs published by the National Medical Products Administration due to its "therapeutic advantages over marketed products."

Clinical trial data for Maviret demonstrate that in treatment-naïve, non-cirrhotic patients with all major hepatitis C virus genotypes (GT1–6), the virologic cure rate exceeds 99%, with a treatment duration as short as 8 weeks. This regimen does not require co-administration of ribavirin and involves once-daily oral dosing. As Maviret is not metabolized by the kidneys, it is suitable for patients with any degree of renal impairment, including those undergoing dialysis, without the need for dose adjustment. In these patients, the virologic cure rate approaches 100%, with a favorable safety profile. (Bioon.com)

Original Source: AbbVie Receives Positive CHMP Opinion for MAVIRET® (glecaprevir/pibrentasvir) to Shorten Treatment Duration to Eight Weeks in Genotype 3, Treatment-Naïve Patients with Chronic Hepatitis C and Compensated Cirrhosis