NORTH CHICAGO, Ill.—AbbVie closed the books on 2013 with some good news, releasing Phase 3 results for its investigational three direct-acting-antiviral (3D) regimen plus ribavirin in patients with chronic, genotype 1 (GT1) hepatitis C virus (HCV) infection.
The SAPPHIRE-II study featured 394 patients, and of those, 96 percent who previously failed pegylated interferon and ribavirin treatment (roughly 49 percent of whom were prior null responders) achieved sustained virologic response (SVR) at 12 weeks with the treatment regimen. Patients with the GT1a subtype saw SVR rates of 96 percent at 12 weeks, with patients in the GT1b subtype seeing rates of 97 percent.
Only 2 percent of patients receiving the regimen saw virologic relapse or breakthrough, and the study had a discontinuation rate due to adverse effects—the most common of which were headache, nausea and fatigue—of only 1 percent (three patients). The results confirm Phase 2 studies, demonstrating a consistent virologic response and tolerability profile, and in light of these results, AbbVie is eyeing a regulatory filing date of the second quarter of 2014.
“SAPPHIRE-II demonstrates that treatment-experienced genotype 1 HCV patients achieved high rates of virologic response with AbbVie’s interferon-free, all-oral 3D regimen plus ribavirin,” Dr. Scott Brun, vice president of pharmaceutical development at AbbVie, said in a news release. “Completion of the two placebo-controlled SAPPHIRE studies is an important step in AbbVie’s HCV clinical development program. We look forward to the results of studies looking at AbbVie’s 3D regimen with and without ribavirin in different patients, as well as data from our dedicated study in patients with cirrhosis.”
SAPPHIRE-II is the second placebo-controlled trial and the second of six Phase 3 trials for AbbVie’s investigational 3D regimen for GT1 hepatitis C patients. GT1 represents the most prevalent genotype in the world, with the United States seeing a higher prevalence of 1a and Europe a higher prevalence of 1b.
AbbVie’s 3D regimen is made up of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267 and non-nucleoside polymerase inhibitor ABT-333, and the three different mechanisms of action are meant to interrupt the HCV replication process to optimize SVR rates. ABT-450 is the result of an ongoing collaboration between AbbVie and Enanta Pharmaceuticals Inc. for HCV protease inhibitors and regimens that include protease inhibitors. The 3D regimen received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) in May of last year.
Hepatitis C is a popular indication these days, as there’s no shortage of potential patients—some 160 million people worldwide are infected with the disease. Efforts of late have been focused on all-oral regimens and regimens with a duration of 12 weeks, as opposed to the current standard of 24 or 48 weeks. As such, AbbVie is racing a few other companies to get the best therapy to market.
Gilead is one of AbbVie’s leading competitors in the market, with a hepatitis C regimen that consists of one pill a day for eight weeks, as opposed to the six pills a day for 12 weeks in AbbVie’s regiment. In three Phase 3 clinical trials of a once-daily fixed-dose combination of the nucleotide analog polymerase inhibitor sofosbuvir 400 mg and the NS5A inhibitor ledipasvir 90 mg, with and without ribavirin, Gilead reported seeing SVR 12 rates of between 93 and 99 percent among the various arms of the trials. In addition, the company announced on December 6 that the FDA had approved Sovaldi (sofosbuvir) 400 mg tablets, a once-daily oral nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen.
BMO Capital Markets analyst Alex Arfaei commented in a research note that despite the downside of consisting of more pills, AbbVie’s regimen “remains underappreciated,” noting that while “Gilead will have a convenience advantage … we do not believe convenience is as important for an eight- to 12-week treatment regimen that produces a cure compared with, for example, chronic HIV treatment.”