Results from the SAPPHIRE-I trial show that Abbvie's 3D therapy produced 96% sustained viral response rates at 12 weeks in treatment-naive patient with genotype 1 hepatitis C.
Might future HCV-G1 patients be able to start their therapeutic journey on a different note by avoiding the treatment-limiting toxicities of current standard of care interferon (INF)-based therapies?
More than 2,700 patients infected with the hepatitis c virus (HCV) have been treated with Abbvie’s “3D” interferon-free combination therapy, made up of ABT-450/ritonavir, ombitasvir (formerly ABT-267), and dasabuvir (with or without ribavirin to date.
Data from the double-blinded, randomised, placebo-controlled SAPPHIRE-I trial, which tested the efficacy and safety of this combination therapy, show it is associated with 96% sustained viral response rates at 12 weeks (SVR12) in treatment-naïve patients with HCV subgenotype 1 (HCV-G1).
The SAPPHIRE-1 trial design included 631 chronic HCV-G1, treatment-naïve, non-cirrhotic patients between the ages of 18 and 70 who had a high viral load. Importantly, these patients did not have HIV co-infection. The majority of the patients were male, white, with an average age of 52, and an average BMI of 25. The majority (2/3) of patients had an unfavourable IL28 genotype.
Patients were randomised (3:1) to receive either active treatment with the 3D interferon-free combination therapy or matching placebos for 12 weeks during the double blind period.
Combination therapy consisted of ABT-450/ritonavir/ABT-267 (150mg/100mg/25mg QD) + dasabuvir (250mg BID) + weight-based ribavirin (1000mg or 1200mg daily divided BID).
Patients in the placebo arm were then rolled over to active treatment for a further 12 weeks with 3D plus ribavirin for an additional 12 weeks. All patients were followed for 48 weeks after their active dosing.
Jordan J. Feld, MD, of the University of Toronto, said, “The results show that this 12-week regimen is a potent and efficacious treatment for HCV-G1 with very good tolerability. The intention-to-treat SVR12 results in the treatment arm were 96.2% (455/475 patients), which was clearly above the non-inferiority and superiority thresholds.”
For HCV-G1a subgroup patients, the SVR12 rates were 95.3% and72% for treatment and control groups, respectively. SVR12 rates for HCV-G1a subgroup patients were 98% and 80% for treatment and control groups, respectively. The treatment breakthrough and relapse rates were 0.2% and 1.5%, respectively. The SVR12 rate was above 90% in all important subgroups such as age, ethnic group, fibrosis stage, age, BMI, or requirement of ribavirin dose modification.
Feld also noted that “although a fairly high percentage of patients in the treatment arm of the trial experienced some type of adverse effect, 70% of patients in the placebo arm also experienced adverse events during the dosing period, the most common adverse events for both treatment and placebo groups being fatigue and headache. Discontinuation due to adverse events was rare accounting for only 3 patients (0.6%).”
Addressing the question of adverse effects, Feld said, “under 1% of treated patients had Grade 3 or 4 laboratory abnormalities during the study (none of which were associated with hepato-toxicity), 5% of patients had anaemia with haemoglobin level down to 10mg/dl, one patient received erythropoietin, and no patients required transfusion.”