Grazoprevir-elbasvir combo pill effective in chronic hep C

Last Updated: 2015-04-24

By Reuters Staff

NEW YORK (Reuters Health) - Treatment with a fixed-dose combination of grazoprevir and elbasvir taken once daily without interferon or ribavirin for 12 weeks yielded high sustained response rates in patients with chronic hepatitis C virus (HCV) genotype 1, 4 or 6 in the phase 3 C-EDGE trial.

The findings were presented today at the European Association for the Study of the Liver annual meeting in Vienna, Austria, and published simultaneously in Annals of Internal Medicine.

The C-EDGE trial enrolled 412 mono-infected treatment-naïve cirrhotic and non-cirrhotic patients with HCV genotype 1, 4, or 6 infection from 60 centers in the United States, Europe, Australia, Scandinavia and Asia. Patients were randomly allocated to immediate or deferred treatment with fixed-dose grazoprevir 100 mg/elbasvir 50 mg once daily for 12 weeks.

Of the 316 patients in the immediate treatment group, 95% had undetectable viral load (sustained virologic response) for 12 consecutive weeks (SVR12) after treatment, report Dr. Stefan Zeuzem from Goethe University Hospital in Frankfurt, Germany, and colleagues.

SVR12 rates were 92% for patients with genotype 1a; 99% for genotype 1b; 100% for genotype 4; and 80% for genotype 6. The drug worked equally well in cirrhotic and non-cirrhotic patients (SVR12 97% and 94%, respectively).

"Subgroup analyses showed no meaningful effects of age, sex, race, ethnicity, or IL28B genotype on treatment outcome but did suggest an effect of higher baseline viral load (>800 000 IU/mL), which appeared to vary by the presence of baseline NS5A resistance-associated variants (RAVs)," the researchers report.

Grazoprevir/elbasvir was generally well tolerated with a similar safety profile in cirrhotic and non-cirrhotic patients and in the active and placebo treatment arms; no serious adverse event was judged to be drug related by site investigators.

The most common adverse events were headache (17%), fatigue (15%), and nausea (9%) and occurred with similar frequencies in cirrhotic and non-cirrhotic patients and in the active and placebo arm.

Late elevations in aminotransferase levels greater than five times the upper limit of normal occurred in four patients (1.3%) in the immediate-treatment group; none was associated with hyperbilirubinemia. "These abnormalities were reversible and had no major clinical consequences," the researchers say.

They conclude, "This once-daily, single-tablet, two-drug combination constitutes a potent new therapeutic option for chronic HCV infection."

The study was sponsored and funded by Merck & Co. Several of the authors have declared financial relationships with the company.

On April 8, Merck announced that grazoprevir/elbasvir received breakthrough-therapy designation from the U.S. Food and Drug Administration (FDA) for treatment of patients with HCV genotype 1 and 4. The company said it "remains on track" for the New Drug Application filing with the FDA by the end of June.

SOURCE: http://bit.ly/1OOCnky

Ann Intern Med 2015.