New Hepatitis C Combination Shows Stellar Results Across All Genotypes

Gilead continues a string of recent successes with stellar data from four late-stage studies showing that a combination featuring its blockbuster polymerase inhibitor sofosbuvir (SOF) (Sovaldi^®) and the experimental NS5A inhibitor velpatasvir (VEF) is effective across all hepatitis C virus (HCV) genotypes.

The finding is potentially important for practitioners and patients alike, because it could eliminate the need for HCV genotype testing prior to treatment. It comes on the heels of a whirlwind couple of years for Gilead, which introduced Sovaldi in late 2013 and its follow-up, Harvoni, late last year. Both have achieved blockbuster status while effectively amounting to a cure for certain genotypes of HCV. Competition has arrived quickly from Abbvie, and is soon to arrive from Merck and others, but this latest finding assures that Gilead will continue to be the standard-bearer in HCV treatment.

According to a press release from Gilead, of the 1,035 patients treated with SOF/VEL for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 (98%) achieved the primary efficacy endpoint of Sustained virologic response at week 12 (SVR12) — defined as an undetectable HCV RNA level 12 weeks after treatment discontinuation. Of the 20 patients who did not achieve SVR12, 13 patients (1.3%) experienced virologic failure and seven did not complete an SVR12 visit (e.g., lost to follow-up). Twelve of the 13 virologic failure patients relapsed (two genotype 1 HCV-infected patients and 10 genotype 3 HCV-infected patients). There was one patient with documented reinfection. No patients with genotype 2, 4, 5 or 6 HCV infection had virologic failure.

The new pangenotype therapy has been given “breakthrough” status drug by the Food and Drug Administration (FDA), which is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates that the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.

Patients treated with SOF/VEL for 12 weeks in these three studies had similar adverse events compared with placebo-treated patients in ASTRAL-1. Two patients (0.2%) treated with SOF/VEL for 12 weeks, one each in ASTRAL-1 and ASTRAL-2, discontinued treatment due to adverse events. The most common adverse events were headache, fatigue, and nausea. In ASTRAL-4, patients with Child-Pugh class B cirrhosis receiving SOF/VEL+RBV achieved higher SVR12 rates than patients receiving SOF/VEL for 12 or 24 weeks. Among genotype 1 and 3 patients treated with SOF/VEL+RBV for 12 weeks, the SVR12 rates were 96% and 85%, respectively.

Preliminary results from the ASTRAL trials were presented at the 2015 Meeting of the European Association for Study of the Liver, but full trial results have not yet been published.