Direct-acting hep C antivirals effective without interferon

HealthDay News — Chronic hepatitis C (HCV) can be effectively treated without any of the standard drugs, two studies show.

Cure rates with all-oral combination treatment consisting of daclatasvir and sofosbuvir (Sovaldi, Gilead) ranged from 89% to 100%,  Mark Sulkowski, MD, of Johns Hopkins University, and colleagues, reported in New England Journal of Medicine.

The regimen worked equally well with or without ribavirin, a mainstay of HCV treatment with unfavorable side effects including hemolytic anemia and teratogenicity, the researchers noted, as well as in patients with previous treatment failure, mutations typically associated with poor treatment response and those with difficult to treat genotypes.

The open-label study involved 211 patients with HCV genotype 1 (previously untreated or with previous virologic failure with telaprevir or boceprevir), genotype 2 or genotype 3 infection.

Participants were randomized to receive daclatasvir plus sofosbuvir with or without ribavirin for 12 or 24 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of therapy (SVR₁₂) — overall, 201 patients met this endpoint. SVR₁₂ rates by patient type were as follows:

• 98% in previously untreated genotype 1 patients and the same in genotype 1 patients who had failed previous therapy with interferon, ribavirin and HCV protease inhibitors
• 92% of patients with genotype 2, and 89% of those with genotype 3 infection
• 98% and 100%, respectively, among patients with HCV subtypes 1a and 1b
• 93% and 98%, respectively, for those with CC and non-CC IL28B genotypes, where the non-CC genotypes are regarded as predicting poor response
• 94% among those who also got ribavirin, and 98% among those who did not

“Once-daily oral daclatasvir plus sofosbuvir was associated with high rates of sustained virologic response among patients infected with HCV genotype 1, 2 or 3,” Sulkowski and colleagues wrote. 

Results of a second open-label phase 2b study published in the journal also yielded promising results for patients treated with triple or quadruple drug regimens. The cohort involved 571 patients with genotype 1 infection divided into 14 treatment subgroups.

Kris Kowdley, MD, of Virginia Mason Medical Center in Seattle, and colleagues, assigned participants to HCV protease inhibitor ABT-450 boosted with ritonavir, the non-nucleoside polymerase inhibitor ABT-333, the NS5A inhibitor ABT-267 and ribavirin for eight, 12 or 24 weeks.

Overall, 83% to 100% of patients across treatment groups achieved the primary endpoint of sustained virologic response at 24 weeks (SVR₂₄). Notably, 88% of patients assigned to an eight week regimen and 95% of those on 12 weeks of therapy reached SVR₂₄.

The most frequent adverse events were fatigue, headache, nausea and insomnia.

“In this phase 2b study, all-oral regimens of antiviral agents and ribavirin were effective both in patients with HCV genotype 1 infection who had not received therapy previously and in those who had not had a response to prior therapy,” Kowdley and colleagues wrote. 

The Sulkowski study was funded by Bristol-Myers Squibb and Pharmasset (Gilead).The Kowdley study was funded by AbbVie.