NORTH CHICAGO, Ill.—AbbVie announced the completion of its Phase 3 clinical program and released results of four additional studies designed to assess AbbVie's investigational all-oral, interferon-free therapy with and without ribavirin (RBV) in patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection. These results confirm previously reported AbbVie data and further demonstrate high sustained virologic response rates 12 weeks post treatment (SVR12) and tolerability in these GT1 patients.
"The outcomes of AbbVie's comprehensive Phase 3 studies in 2,300 patients across 25 countries demonstrate how our investigational regimen performs across a broad spectrum of genotype 1 patients, including those with compensated liver cirrhosis," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "The high rates of response and tolerability of our regimen, coupled with the low rates of discontinuation are promising."
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral regimen with and without ribavirin with the goal of producing high SVR rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis, the company explained in a press release.
ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of HCV.
The Motley Fool reported that shares of Enanta Pharmaceuticals, a developer of small-molecule drugs to treat infectious diseases, rallied as much as 18 percent after it and development partner AbbVie reported positive results from its late-stage hepatitis C trial involving AbbVie's direct-acting antiviral combo.
The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once daily, and ABT-333 (250mg) with or without ribavirin (weight-based), dosed twice daily. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations.
In May 2013, AbbVie's regimen with and without ribavirin for HCV GT1 was designated as a Breakthrough Therapy by the U.S. Food and Drug Administration (FDA). AbbVie is on track to begin major regulatory submissions early in the second quarter of 2014. AbbVie will disclose detailed study results at future scientific congresses and in publications.
AbbVie has conducted studies in both treatment experienced and treatment-naïve patients. For example, the PEARL-II Phase 3 study is a global, multi-center, randomized, open-label, controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie's regimen with and without ribavirin in non-cirrhotic, GT1b HCV-infected, treatment-experienced adult patients. The study population consisted of 179 GT1b treatment-experienced patients with no evidence of liver cirrhosis: 91 patients randomized to the regimen without ribavirin for 12 weeks, and 88 patients randomized to the regimen with ribavirin for 12 weeks. In the ribavirin-free arm, 100 percent (n=91/91) of patients achieved SVR12, while 97 percent (n=85/88) achieved SVR12 in the ribavirin-containing arm.
The most commonly reported adverse events were fatigue and headache. Discontinuations due to adverse events were reported in none of the patients in the ribavirin-free arm and two (2 percent) patients in the ribavirin-containing arm. There were no patients in either arm of the study that experienced virologic relapse or breakthrough.
The PEARL-III study is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie's regimen with and without ribavirin in non-cirrhotic, GT1b HCV-infected, treatment-naive adult patients.
The study population consisted of 419 GT1b treatment-naive patients with no evidence of liver cirrhosis: 209 patients randomized to the regimen without ribavirin for 12 weeks, and 210 patients randomized to the regimen with ribavirin for 12 weeks. Following 12 weeks of treatment, 99 percent receiving the regimen without ribavirin (n=207/209) and 99 percent receiving the regimen with ribavirin (n=209/210) achieved SVR12.
The most commonly reported adverse events were headache and fatigue. No patient discontinued study drug due to adverse events. Virologic relapse or breakthrough was noted in none of the patients receiving the regimen without ribavirin and 0.5 percent of patients receiving the regimen with ribavirin. Four additional studies reported similar results with SRV12 being achieved in 90 percent or more of the patients.
Globally, about 160 million people are chronically infected with hepatitis C. AbbVie's multinational HCV program is the largest all-oral, interferon-free clinical program in GT1 patients being conducted to date, according to a comparison made by AbbVie based on their review of data from www.clinicaltrials.gov for Phase 3a programs of Gilead, Bristol-Myers Squibb and Boehringer Ingelheim. GT1 (with subtypes 1a and 1b) is the most prevalent genotype worldwide.
As a cautionary footnote, AbbVie points out that Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.