Multiple study results indicate safety, efficacy of sofosbuvir in HCV patients

BOSTON — Sofosbuvir administered with ribavirin can effectively and safely treat patients with various genotypes of hepatitis C, according to several studies presented at The Liver Meeting.

In the phase 2b ATOMIC study, researchers evaluated 332 treatment-naive, noncirrhotic patients with HCV genotype 1 who received 400 mg sofosbuvir with pegylated interferon and ribavirin once daily for 12 weeks (group A; n=52), 24 weeks (group B; n=125, including 16 with genotype 4 or 6) or for 12 weeks followed by 12 more weeks of 400 mg sofosbuvir with or without ribavirin (group C; n=155). The cohort had a mean baseline HCV RNA of 6.4 log₁₀ IU/mL.

Rapid virological response (RVR) occurred in 97% of patients, including 94% of group A, 98% of genotype 1 patients and 100% of genotype 4 or 6 patients in group B, and 97% of group C. Upon completion of treatment, 99% of participants had RNA levels below 15 IU/mL.

Sustained virologic response (SVR) at 12 weeks occurred in 90% of group A patients, 89% of genotype 1 and 81% of genotype 4 or 6 group B patients and 88% of group C patients. SVR24 occurred in 85% of group A patients. No patients experienced virologic breakthrough during treatment, and no relapses occurred between SVR12 and SVR24. Investigators said therapy was well-tolerated, with a safety profile similar to peginterferon with ribavirin.

“Sofosbuvir 400 mg once daily, in combination with peginterferon and ribavirin for 12 weeks appears to be safe and highly effective for the treatment of HCV genotype 1,” researcher Tarek Hassanein, MD, Southern California Liver Centers, Coronado, Calif., said, adding that a 12-week regimen was as effective as 24 weeks of therapy for genotype 1 patients, while patients with genotypes 4 and 6 also benefited from the 24-week regimen.

The ELECTRON trial

In separate results presented by other researchers for the ELECTRON trial, 1,000 mg sofosbuvir and 1,200 mg ribavirin were assigned for 12 weeks to 10 prior null responders with HCV genotype 1, 25 treatment-naive patients with genotype 1, and 25 previously treated genotype 2 or 3 patients. Twenty-five treatment-naive patients with genotype 2 or 3 received a similar dose for 8 weeks, and 10 treatment-naive patients with genotype 2 or 3 received 800 mg sofosbuvir and ribavirin for 12 weeks.

RVR occurred in all participants excluding those in the 800-mg group, and no incidence of viral breakthrough or discontinuation occurred across the cohort. The majority of treatment-naive patients with genotype 1 experienced SVR4 (88%) and SVR12 (84%), and 75% of evaluable and previously treated patients with genotype 2 or 3 experienced SVR4. SVR12 was achieved by one patient in the prior null-response group; the remaining nine experienced relapse before 4 weeks post-treatment.

Additional analysis was performed on a cohort of 25 treatment-naive patients and a smaller group of null-responders who received sofosbuvir with a weight-based ribavirin dose and 90 mg GS-5885, an NS5A inhibitor, for 12 weeks. After 4 weeks of treatment, all patients excluding one null responder had undetectable HCV RNA levels. All treatment-naive patients experienced SVR4. At presentation, three null responders had reached 4 weeks post-treatment, and all had achieved SVR4.

The SPARE trial

In a late-breaking session, a third group of researchers presented results from the SPARE trial, a study of 60 treatment-naive patients with HCV genotype 1 conducted in two arms. In the first, 10 patients with early-stage fibrosis received 400 mg sofosbuvir and weight-based ribavirin (1,000 mg for patients less than 75 kg and 1,200 mg for patients 75 kg or more) once daily for 24 weeks. The remaining patients, with any stage of compensated liver disease, randomly received 400 mg sofosbuvir with either 600 mg ribavirin (n=25) or a full dose (n=25) for 24 weeks in the second arm.

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Apart from one participant who dropped out at week 3, all patients in the first phase experienced end-of-treatment response (ETR), SVR4, SVR8 and SVR12. All patients in the second phase experienced ETR, with 75% of evaluable patients in the full-dose arm and 64% of those in the low-dose arm achieving SVR4. SVR12 data was unavailable at the presentation. No serious adverse events occurred during the study, and no patients discontinued treatment due to adverse events. Multivariate analysis indicated no independent predictors for relapse, but trends were observed for patients with high RNA levels and advanced fibrosis, as well as those in the low-dose ribavirin group.

“In this inner-city, largely minority population of HCV genotype 1 subjects, an interferon-free regimen of GS-7977 was well-tolerated and effective in achieving SVR,” researcher Anu Osinusi, MD, Laboratory of Immunoregulation, NIAID, NIH, said. “Ongoing analysis is currently focused on identifying biologic correlates of HCV clearance, as well as identifying the mechanisms of relapse.”

Disclosure: Researchers for the ATOMIC and ELECTRON trials reported numerous financial disclosures.

For more information:

Hassanein T. #230: Once Daily Sofosbuvir (GS-7977) plus PEG/RBV: High Early Response Rates Are Maintained During Post-Treatment Follow-up In Treatment-Naive Patients With HCV Genotype 1, 4 and 6 Infection in the ATOMIC Study. Presented at: The Liver Meeting 2012; Nov. 9-13, Boston.

Gane EJ. #229: Once Daily Sofosbuvir (GS-7977) Plus Ribavirin In Patients With HCV Genotypes 1, 2 and 3: The ELECTRON Trial. Presented at: The Liver Meeting 2012; Nov. 9-13, Boston.

Osinusi A. LB-4: High Efficacy Of GS-7977 In Combination With Low or Full dose Ribavirin for 24 weeks In Difficult To Treat HCV Infected Genotype 1 Patients: Interim Analysis From The SPARE Trial. Presented at: The Liver Meeting 2012; Nov. 9-13, Boston.