Published: Nov 4, 2013
Coverage of Hepatitis C Virus is supported in part by an independent educational grant from AbbVie Pharmaceuticals.
By Michael Smith, North American Correspondent, MedPage Today
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- This was an open-label, uncontrolled study of two novel direct-acting anti-HCV agents demonstrated high rates of remission 12 weeks post therapy.
- Be aware that all subjects had genotype 1b, which may carry a more favorable response to treatment than genotype 1a
WASHINGTON -- An investigational two-drug combination treatment for hepatitis C (HCV) -- using none of the standard medications -- led to cures in 90% or more of a selected group of patients, a researcher said here.
In an industry-sponsored clinical trial, the drugs reduced the viral load to an undetectable level 12 weeks after the end of treatment (the so-called SVR12) in 95.2% of patients who had never been treated for the virus, according to Eric Lawitz, MD, of the University of Texas Health Science Center in San Antonio.
Among patients who had been previously treated but failed to respond, the SVR12 rate was 90%, Lawitz reported at the annual meeting of the American Association for the Study of Liver Diseases.
While the results look good, it's important to realize the study was small and only included people with one of the HCV genotypes, cautioned Gary Davis, MD, of Baylor University Medical Center, who was not involved in the study but who moderated the session at which it was presented.
Because of that, the findings are not easily generalizable to the whole universe of HCV patients, he told MedPage Today.
But interferon -- a general immune system booster -- is regarded as both difficult to take and dangerous, while ribavirin, a general antiviral, has its own suite of adverse effects, including anemia, that make it difficult to tolerate.
So investigators have been searching for so-called direct-acting agents -- drugs that target aspects of the virus itself -- that would be sufficiently powerful to cure the disease.
In the PEARL-1 study, Lawitz and colleagues studied ABT-450/r, an HCV NS3/4A protease inhibitor boosted with the protease inhibitor ritonavir (Norvir), and ABT-267, which blocks the viral nonstructural protein NS5A.
In an earlier study, the two drugs showed promise with and without ribavirin; the current study is intended to test how well they will do without the older drug.
Lawitz presented results for 82 patients with genotype 1b infection (with or without cirrhosis) treated for 12 weeks. Data for other patient groups is to be presented later, he said.
The primary endpoint of the study was the proportion of patients who reached an SVR12 -- defined as no detectable virus 12 weeks after stopping treatment.
He reported that 41 of the 42 treatment-naive patients had no detectable virus at the end of treatment and 40 reached the SVR12; the two who did not were lost to follow-up rather than suffering virologic failure..
Moreover, 39 of 40 null responders had no detectable virus at the end of treatment and 36 reached SVR12; one patient had viral breakthrough during therapy and three relapsed, Lawitz said.
The regimen was generally well tolerated, he said -- the most common adverse event was headache -- there were no serious adverse events related to the study drugs, and no patients stopped treatment because of adverse events or abnormal laboratory findings.
The study was supported by AbbVie. Lawitz reported financial links with AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Idenix Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Merck & Co, Novartis, Presidio, Roche, Santaris Pharmaceuticals, Vertex Pharmaceuticals, Kadmon, Achillion Pharmaceuticals, BioCryst, Biotica, Enanta, Idenix, and Theravance. Several authors are employees of AbbVie.
Davis reported financial links with Abbott, Bristol-Myers Squibb, Boehringer Ingelheim, Genentech, Gilead, Johnson&Johnson, Merck & Co, Novartis, Pharmasset, and Vertex.
Primary source: American Association for the Study of Liver Diseases
Source reference: Lawitz E, et al "Interferon- and ribavirin-free regimen of ABT-450/r + ABT-267 in HCV genotype 1b-infected treatment-naïve patients and prior null responders" AASLD 2013; Abstract 75.