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Reuters Health Information (2013-03-27): Early test of micro-RNA-targeting drug shows promise against HCV

Drug & Device Development

Early test of micro-RNA-targeting drug shows promise against HCV

Last Updated: 2013-03-27 17:12:17 -0400 (Reuters Health)

NEW YORK (Reuters Health) - The Santaris Pharma drug miravirsen significantly reduced blood levels of hepatitis C virus (HCV) and, in a few cases, kept the virus at undetectable levels 14 weeks after treatment stopped, according to new research funded by the manufacturer.

The study, released online today in the New England Journal of Medicine, was a phase IIa trial that focused on patients with chronic HCV genotype 1 infection and involved a new technique for clearing the virus.

The drug, formerly known by its experimental name SPC3649, blocks the access to microRNA-122 (miR-122), which is active in liver cells and required by the virus to replicate. Similar chunks of microRNA regulate cell activity throughout the body.

When microRNA-122 was blocked, the hepatitis virus couldn't function properly and, in some cases, began to disappear from the blood.

"The reduction in HCV RNA levels was dose-dependent and sustained beyond the administration period for miravirsen," the researchers reported. They said a reduction in HCV RNA of at least 2 log(10) IU/mL occurred in one patient (11%) receiving 3 mg/kg of miravirsen and in six patients each (67%) in the groups receiving 5 or 7 mg, compared to placebo.

"This is a big step forward for hepatitis C but it's a bigger step forward for medicine in general because it's the first study to show that, in humans, blocking microRNA can have good efficacy" with few apparent side effects, said chief author Dr. Harry Janssen of the University of Toronto.

Because cancer, heart, nerve and metabolic diseases may also involve microRNA, he said in a telephone interview from Shanghai, "this study opens up different avenues of treatment for these types of diseases."

Dr. Kenneth Sherman, a hepatitis researcher at the University of Cincinnati College of Medicine who was not involved in the study, told Reuters Health by email that miravirsen "represents an exciting new therapeutic class of drugs for this serious and common liver disease."

"The absence of interactions with other drugs, combined with what appears to be a high barrier to resistance, makes this approach very desirable," he said. Other hepatitis C drugs are being developed, but "these data suggest that miravirsen could play an important role in our future armamentarium against a virus that causes progressive liver disease in millions of people worldwide."

Dr. Janssen's team gave five weekly doses of the drug or placebo to 36 volunteers.

All initially had virus levels ranging from about 5 to 7, using a logarithmic scale. Placebo recipients showed virtually no improvement.

Miravirsen worked better in some volunteers than others, which Dr. Janssen said wasn't surprising.

"The treatment targets the host, not the virus. And in many of these host-targeting treatments you see a heterogeneous response rate," he said.

Of the nine patients who received the lowest dose of 3 mg/kg each week, the five people with the best outcomes also received established treatment with pegylated interferon and ribavirin during the observation period.

At the highest dose of 7 mg/kg, nearly everyone saw some decline in virus levels. Five patients saw their virus levels drop into the undetectable range, but in two of those cases the levels rebounded during the observation period.

Most of those getting 5 mg/kg also had initial reductions and some rebounds. Only one of the nine volunteers in that group ended up with virus levels in the undetectable range.

Taken together, all three treatment groups saw a rebound, with peak effectiveness coming at week seven in the 3 mg/kg group, week 12 in the 5 mg/kg group and weeks eight to 10 for the 7 mg/kg group.

There were no side effects that seemed connected to the treatment.

Problems such as headache and fatigue were experienced by placebo recipients at comparable levels. For example, flu-like symptoms were seen in two patients in the low-dose group, none in the medium-dose group and one in both the high-dose and placebo groups.

No doses were reduced because of side effects.

As seen in previous studies, the drug also produced a gradual and prolonged reduction in cholesterol.

The researchers are currently testing whether it is better to give miravirsen for 12 weeks instead of five.

"All tested strains of HCV depend on miR-122, suggesting that it is a universal HCV Achilles' heel," said Dr. Judy Lieberman of Harvard Medical School and Dr. Peter Sarnow of Sanford University in an online editorial.

Such drugs, alone or in combination, they said, "could provide curative therapy for a large proportion of patients infected with all HCV strains without danger of drug resistance. It could also shorten the treatment time to achieve viral elimination, reduce the rate of relapse, and offer the possibility of interferon-free regimens. Only further clinical trials can determine whether this promise can be met."


N Engl J Med 2013.

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