HBV drug well tolerated, reduces surface antigens in phase 2 trial
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Patients with hepatitis B treated with an investigational RNAi drug experienced reduced levels of surface antigens across different dose levels, according to research presented at The Digital International Liver Congress.
The drug, called VIR-2218 (VIR Biotechnology), is an X-targeting RNAi therapeutic designed to silence all HBV transcripts across all 10 HBV genotypes.
“GaINAc conjugation allows targeted delivering to the liver through subcutaneous administration and prolongs the pharmacodynamic effects of VIR-2218, thereby allowing monthly dosing,” Edward Gane, MD, from the University of Auckland in New Zealand, said in his presentation.
In the study, patients with both e-antigen negative and positive HBV on nucleos(t)ide reverse transcriptase therapy received two doses of VIR-2218 (n = 24) or placebo on day 1 and day 29. Two cohorts of patients with HBeAg+ received either 50 or 200 mg of the drug. Four cohorts of patients with HBeAg– received either 20, 50, 100 or mg of the drug, two cohorts were added later at the 50 and 200 mg dose levels.
Within each cohort, three patients received VIR-2218 and one received placebo. Investigators assessed safety and hepatitis B surface antigen levels at 12 weeks after the second dose and followed patients for an additional 32 weeks if they met HBsAg decline targets.
Researchers found that in a subset of patients in the 50 mg dose cohort achieved a maximal decline in HBsAg levels at week 12, with a mean decline of 1.5 logs from baseline. They also observed declines in HBsAg in the other cohorts with patterns of both early and delayed responses.
“The higher the dose, the greater surface antigen reduction,” Gane said. “Secondly, the higher the dose, the more delayed the post-treatment virologic rebound. Finally, thirdly, the higher the dose, the greater proportion of patients who achieved surface antigen below 100 international units per mil.”
Gane said that no patients had to discontinue therapy due to an adverse event, and the majority of adverse events were mild in severity.
“These results support the potential of VIR-2218 as the backbone of a finite treatment regimen aiming at a functional cure for patients with chronic hepatitis B,” Gane said.
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Gane E, et al. Abstract AS068. Presented at: The Digital International Liver Congress; Aug. 27-29.
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