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Miravirsen safe, effective among patients with chronic HCV

Patients with chronic hepatitis C genotype 1 treated with miravirsen experienced dose-dependent reductions in HCV RNA compared with placebo recipients in a recent study.

In a phase 2a international study, researchers randomly assigned 36 adults with chronic HCV genotype 1 to receive subcutaneous injections of microRNA-122 (miR-122) inhibitor miravirsen at 3 mg/kg, 5 mg/kg or 7 mg/kg or placebo five times a week for 29 days (n=9 for each group). No participants had received previous HCV treatment.

Treated patients experienced a mean maximum reduction of HCV RNA of 1.2 log₁₀ IU/mL in the 3-mg group (P=.01), 2.9 log₁₀ IU/mL in the 5-mg group (P=.003) and 3.0 log₁₀ IU/mL in the 7-mg group (P=.002), compared with 0.4 log₁₀ IU/mL among placebo recipients. Undetectable HCV RNA levels were observed in one patient from the 5-mg group and four from the 7-mg group. Two participants continued to have undetectable levels at 14 weeks, with one continuing through 18 weeks. Virologic rebound occurred in one 3-mg recipient, five 5-mg recipients and three 7-mg recipients. No resistance-associated mutations were observed.

Treated patients experienced 112 adverse events; placebo recipients experienced 31. After therapy, one 7-mg patient lost consciousness, but no patients stopped miravirsen or required dose limiting. Investigators noted a decrease in serum ALT levels among treated recipients.

“Our results are relevant to the consideration of miravirsen as a potential treatment for HCV infection,” the researchers wrote. “The strategy … may also be relevant for diseases other than chronic HCV infection. Within the field of hepatology, the inhibition of miR-122 has been associated with an improvement of steatosis in a mouse model of diet-induced obesity, suggesting a role for miR-122 antagonism in the treatment of [NAFLD]. Within other fields, therapeutic silencing of disease-associated miRNAs in preclinical studies of cancer and of cardiovascular and autoimmune disorders has delivered results that warrant clinical investigation.”

Disclosure: See the study for a full list of relevant disclosures.