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Oligonucleotide injection reduced HCV viral load

VIENNA — Injection of an oligonucleotide with activity against microRNA-122 led to undetectable viral load in a cohort of HCV patients of multiple genotypes, according to data presented in the Late Breakers session at the 2015 International Liver Congress.

Meike Van Der Ree, MD, of the department of gastroenterology and hepatology at the Academic Medical Center, Amsterdam, said that microRNA-122 is an important host factor in the replication of HCV virus. She said that when it binds to HCV 5’-UTR RNA, the immune response to the virus is inhibited.

“RG-101 is a hepatocyte targeted carbohydrate conjugated oligonucleotide with potent antagonist activity against miR-122,” she said during the Late Breakers session.

The phase 1 study included 16 patients with genotype 1 disease, 10 patients with genotype 3 and six patients with genotype 4 HCV. There were 23 treatment-naive patients, nine patients who had relapsed after interferon-based therapy and none with cirrhosis.

Clinicians injected 14 patients with one administration of 2 mg/kg RG-101 and two patients with placebo. A second cohort included 14 more patients who received one administration of 4 mg/kg of the study drug and two more patients received placebo.

“RG-101 is rapidly cleared from plasma during the first 24 hours post dose,” Van Der Ree said.

The researchers initially followed patients for 8 weeks.

They observed a number of adverse events, but few related to the study drug. These were mostly mild and transient in nature: five injection site reactions, one complaint of abdominal pain, one case of dry mouth and one case of increased conjugated bilirubin.

“The majority of events were mild and transient and not related to the study drug,” Van Der Ree said. “There was no change in hematological or renal laboratory values.”

Van Der Ree noted that most patients experienced decreases in ALT and AST levels after RG-101 dosing.

At week 8, 15 of 28 patients (54%) had HCV RNA levels below the limit of quantification.

Due to the positive outcomes, the researchers extended the follow-up period and interim results were reported at week 20.

At week 12, 10 patients had HCV RNA levels that were below the limit of quantification and at 20 weeks, 70% of those patients (7/10) were still below the limit of quantification.

Van Der Ree reported that all patients treated with RG-101 responded and that reductions in HCV RNA levels were observed in all of the genotypes studied. She suggested that this injection regimen may be considered for combination with oral agents and also for monotherapy in certain underserved patient populations with HCV. – by Rob Volansky

For More Information:

Van Der Ree M. Abstract L07. Presented at: International Liver Congress; April 22-26, 2015; Vienna.

Disclosure: Van Der Ree reports no relevant financial disclosures.

Editor's note: This article has been updated with clarification from the presenter.