Enanta Pharmaceuticals to present detailed results from AbbVie’s pivotal Phase III SAPPHIRE-I study

Results from the SAPPHIRE-II study were presented at the congress on 10 April 2014. Additionally, results from both the SAPPHIRE-I and SAPPHIRE-II studies have been published on-line in the New England Journal of Medicine.

The SAPPHIRE-I and SAPPHIRE-II studies report results from AbbVie’s investigational three direct-acting antiviral regimen containing ABT-450, Enanta’s lead protease inhibitor developed through Enanta’s collaboration with AbbVie. The regimen consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333.

In the SAPPHIRE-I (N=631) and SAPPHIRE-II (N=394) placebo-controlled studies, adult, non-cirrhotic patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection receiving the investigational three-direct-acting antiviral regimen with ribavirin (RBV) for 12 weeks achieved sustained virologic response rates 12 weeks post-treatment (SVR12) of 96.2% (n=455/473) and 96.3% (n=286/297), respectively.

In SAPPHIRE-II, treatment-experienced sub-populations randomized to the three direct-acting antiviral regimen with RBV in the study were prior null responders (49.2%), prior relapsers (29.0%) and prior partial responders (21.9%) to pegylated interferon and RBV.

In SAPPHIRE-I, high response rates were seen across patients with certain variable characteristics, including gender, race, body mass index, fibrosis stage and baseline HCV viral load, as some of these patients have historically had a reduced response to treatment.

Discontinuations due to adverse events were reported in 0.6 percent of patients in both arms in SAPPHIRE-I and in 1.0% of patients receiving the AbbVie regimen in SAPPHIRE-II and no patients receiving placebo.

The most commonly reported treatment-emergent adverse events (>10% in either arm) for both SAPPHIRE-I and SAPPHIRE-II were fatigue, headache, nausea, asthenia, insomnia, pruritus and diarrhea. Additional common adverse events occurring in the studies were rash in SAPPHIRE-I and dyspnea, cough and myalgia in SAPPHIRE-II.

In SAPPHIRE-I, the adverse events that occurred with a significantly greater frequency in the treatment arm compared to placebo were pruritus, insomnia, diarrhea, nausea and asthenia; in SAPPHIRE-II, only pruritus.

SAPPHIRE-I is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with the three direct-acting antiviral regimen with RBV in non-cirrhotic, GT1a and GT1b HCV-infected adult patients new to therapy.

The study population consisted of 631 patients: 473 were randomized to the three direct-acting antiviral regimen with RBV for 12 weeks, and 158 patients were randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the AbbVie regimen with RBV for 12 weeks.

Of the 473 patients randomized to the three direct-acting antiviral regimen with RBV, one case (0.2%) of on-treatment virologic failure occurred and seven patients (1.5%) experienced post-treatment relapse. In addition, three patients (0.6%) were lost to follow-up and seven patients (1.5 percent) discontinued the study prematurely. Patients lost to follow-up were considered treatment failures.

SAPPHIRE-II is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with the three direct-acting antiviral regimen with RBV in non-cirrhotic, GT1a and GT1b HCV-infected, treatment-experienced adult patients who previously failed treatment with pegylated interferon and RBV.

The study population consisted of 394 patients: 297 were randomized to the three direct-acting antiviral regimen with RBV for 12 weeks, and 97 patients were randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the three direct-acting antiviral regimen with RBV for 12 weeks.

Of the 297 patients randomized to the three direct-acting antiviral regimen with RBV, there were no cases of on-treatment virologic failure and seven patients (2.4%) experienced post-treatment relapse.

Of these patients, six were prior null responders and one was a prior relapser. Three patients (1.0%) prematurely discontinued therapy due to adverse events and one patient (0.3 percent) prematurely discontinued the study.