By Michael Smith, North American Correspondent, MedPage Today
Published: November 12, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
SAN FRANCISCO -- A novel hepatitis C virus (HCV) drug targeting genetic material in the liver was safe and well tolerated in a small, dose-finding clinical trial, a researcher said here.
Given as monotherapy, the compound, dubbed miravirsen, induced rapid dose-dependent reductions in the hepatitis C viral load, according to Harry Janssen, MD, of Erasmus Medical Center in Rotterdam, the Netherlands.
The reductions were sustained for more than a month after the end of therapy, Janssen reported at a late-breaker session during the annual meeting of the American Association for the Study of Liver Diseases.
Miravirsen "has the potential to eradicate" hepatitis C virus either alone or as part of an interferon-free regimen, Janssen concluded.
The compound blocks a host microRNA -- miR-122 -- that is critical to hepatitis C accumulation in the liver, Janssen said. MicroRNAs play important roles in gene regulation and expression and Janssen said miravirsen is the first drug to exploit a microRNA target for therapy.
Indeed, of the research presented at the late-breaker session, this study is " the most exciting because it is a whole new class of drug," said Norah Terrault, MD, of the University of California San Francisco, who was not part of the study but who was one of the moderators of the session.
For the study, Janssen said, researchers enrolled 36 patients with the difficult-to-treat genotype 1 of hepatitis C and assigned them to placebo or one of three doses of the drug -- 3, 5, and 7 mg/kg.
The patients, none of whom had been previously treated with pegylated interferon and ribavirin, were given five subcutaneous injections of the drug over four weeks and then followed for another 14 weeks.
The primary endpoint was safety and tolerability, Janssen said, with viral response as a second endpoint. Not all patients have completed the study, so the researchers reported data up to week 10, six weeks after the final dose.
Adverse events, he said, were "very much balanced" among the arms and over all "there were not a lot of side effects seen here." Most such events were mild and none led to stopping treatment, he added.
The only serious adverse event, in a patient receiving the high dose of the drug, was not considered related to treatment, he said.
In all three arms, the drug resulted in a significant drop in hepatitis C RNA levels, compared with placebo. Specifically:
• The low dose (3 mg/kg) led to a 0.57 IU/mL decline in viral load, which was significant at P=0.0334.
• The medium dose (5 mg/kg) yielded a drop of 2.16 IU/mL, which was significant at P=0.007.
• The high dose (7 mg/kg) led to a decline of 2.73 IU/mL, significant at P<0.001.
Although some patients in the low- and medium-dose arms had been allowed to begin treatment with peginterferon and ribavirin three weeks after their last dose of miravirsen, those taking the high dose were not allowed standard therapy until week 10.
Janssen said the drop in viral load seen with the high dose at week 10 "is a pure effect of miravirsen."
The downside of the drug, Terrault told MedPage Today, is that "it has to be given by injection, and that's always a challenging form of treatment."
On the other hand, it appears well tolerated and safe, with good efficacy, so "it might still be part of the mix" of treatment options. "I clearly get the sense it isn't going to be used solo," she said.
The study was supported by Santaris Pharma. Janssen reported financial links with the company and one author was employed by the company.
Terrault reported financial links with Gilead, Pfizer, Genentech, Roche, SciClone, BMS, Novartis, Eisai, and Vertex.
Primary source: Hepatology
Janssen HL, et al "A randomized, double-blind, placebo (PLB) controlled safety and anti-viral proof of concept study of miravirsen (MIR), an oligonucleotide targeting miR-122, in treatment naive patients with genotype 1 (GT1) chronic HCV infection" Hepatology 2011; Abstract LB-6.