• Viral Infections
• Hepatology Clinical Trials
• Liver Conditions

• Hepatology
• Viral Infections
• Hepatology Clinical Trials
• Liver Conditions

An oral, once-daily, fixed-dose combination of the nucleotide polymerase inhibitor sofosbuvir (SOF) and nonstructural protein 5A (NS5A) inhibitor GS-5816 (ledipasvir) provided for 8 weeks with or without ribavirin to noncirrhotic patients infected with hepatitis C virus (HCV) genotype 3 (GT-3) yields high rates of sustained virological response 12 weeks after therapy (SVR12). The final results of the phase 2 ELECTRON-2 study were presented by Edward Gane, MD, Auckland Clinical Studies, Auckland, New Zealand.

SOF has potent activity against HCV [Jacobson IM et al. New Engl J Med. 2013; Lawitz E et al. New Engl J Med. 2013]. Unpublished studies presented at the European Association for the Study of the Liver annual meeting have also indicated the anti-HCV activity of GS-5816, and the high SVR following a 12-week regimen in noncirrhotic, treatment-naïve HCV patients. These studies spurred the phase 2, open-label, ELECTRON-2 study evaluating the efficacy and safety of an 8-week regimen of SOF + GS-5816 in noncirrhotic, treatment-naïve patients infected with HCV GT-3. The primary efficacy end point was SVR12 with a lower limit of quantitation of HCV RNA of 15 IU/mL. The primary safety end points were adverse events and laboratory abnormalities.

Subjects received SOF + GS-5816 25 mg (n = 27), SOF + GS-5816 25 mg along with ribavirin (n = 24), SOF + GS-5816 100 mg (n = 27), or SOF + GS-5816 100 mg along with ribavirin (n = 26). The baseline demographics of the 4 study arms were comparable.

The viral kinetics of the 4 arms were similar, with HCV RNA descending to undetectable levels by week 2 of treatment. SVR12 for the SOF + GS-5816 25 mg arm was 100% (27/27) in the absence of ribavirin and 88% (21/24; 2 relapses and 1 discontinuation due to adverse event prior to decline of HCV RNA to an undetectable level) in the presence of ribavirin. SVR12 for the SOF + GS-5816 100 mg arm was 96% (26/27; consent withdrawn in 1 patient) in the absence of ribavirin and 100% (26/26) in the presence of ribavirin.

Adverse events were least frequent in the SOF + GS-5816 25 mg arm (18/27; 67%) compared with SOF + GS-5816 25 mg + ribavirin (19/24; 79%), SOF + GS-5816 100 mg (22/27; 81%), and SOF + GS-5816 100 mg + ribavirin (22/26; 85%). One serious adverse event occurred in the SOF + GS-5825 25 mg arm; it was not treatment related (noncompliance with seizure medication, seizure occurring after completing treatment). Adverse events occurring in more than 10% of patients were mild to moderate, similar in frequency between arms, and mainly comprised fatigue, headache, and nausea.

Ribavirin-containing treatments produced a decline in mean hemoglobin from weeks 2 to 8. Following treatment completion, the levels increased and were comparable with the other treatment arms.

The use of SOF + GS-5816 at 25 or 100 mg with or without ribavirin for 8 weeks yielded high SVR12 rates in treatment-naïve, noncirrhotic patients with HCV GT-3 infection. No virologic failures occurred in those receiving SOF + GS-5816 100 mg. Treatment was well tolerated. The results have prompted a phase 3 trial that will evaluate a ribavirin-free, fixed-dose combination of SOF 400 mg and GS-5816 100 mg.

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