This article is more than 5 years old. Information may no longer be current.

Alisporivir plus ribavirin yields high response rates for HCV genotype 3

In the VITAL phase 2b study, alisporivir plus ribavirin yielded high sustained virologic response rates for patients with hepatitis C genotype 3 infection with early viral clearance, according to published study data.

“[HCV] genotypes 2 and 3 previously were considered collectively as ‘easy to treat’ with pegylated [interferon] and ribavirin,” the researchers wrote. “However, sustained virologic response rates are consistently lower for patients infected with genotype 3 compared with genotype 2 … and are not improved by extending [pegylated interferon] plus ribavirin treatment duration from 24 to 48 weeks.”

Researchers randomly assigned 340 noncirrhotic patients to a dosage of alisporivir (Debio 025, Debiopharm Group; ALV) at 1,000 mg once daily, ALV at 600 mg once daily with ribavirin, ALV at 800 mg once daily with ribavirin, ALV at 600 mg with PEG-IFN or PEG-IFN and ribavirin for 24 weeks. Patients receiving IFN-free ALV regimens who achieved rapid virologic response (RVR) continued the same treatment throughout the entire study, whereas those who were positive for HCV RNA at 4 weeks received ALV, ribavirin and PEG-IFN from 6 to 24 weeks.

Overall, 300 patients were dosed with an ALV regimen. In these patients, the intent-to-treat rates of SVR at 24 weeks after treatment were higher compared with patients who received just PEG-IFN with ribavirin (80% to 85% vs. 58%).

Patients with genotype 3 had higher RVR rates compared with genotype 2 patients undergoing treatment with ALV, without PEG-IFN (31% vs. 22%). In addition, patients with genotype 3 had higher SVRs to treatment with ALV without PEG-IFN.

Per-protocol analysis showed higher SVR24 rates in patients who received ALV with ribavirin after RVR compared with alisporivir alone after RVR and PEG-IFN with ribavirin (92% vs. 72% vs. 70%), respectively.

Three percent of the patients experienced viral breakthrough. Patients who underwent ALV treatment showed better safety and tolerability compared with patients on regimens containing PEG-IFN. The mean number of adverse events per patient was lower among those who received ALV compared with patients on an interferon-based regimen (2-3.4 vs. 5.2-8.6). Six percent of patients experienced serious adverse events, such as infection and gastrointestinal disorders, and led to three patients discontinuing treatment.

“Alisporivir plus ribavirin represents an effective IFN-free option for a proportion of patients with HCV genotype 2 or 3 infections, with high SVR rates for patients with early viral clearance,” the researchers concluded. “Further investigations of alisporivir in IFN-free combination regimens with direct acting antiviral drugs deserve exploration in future trials.” – by Melinda Stevens

Disclosures: Pawlotsky reports receiving consulting and lecturing fees from AbbVie, Achillion, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck and Novartis, and research support from Gilead. Please see the full study for a list of all other authors’ relevant financial disclosures.