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Vesatolimod safe, well-tolerated in patients with chronic HBV

Vesatolimod was safe and well-tolerated in patients with chronic hepatitis B and demonstrated consistent dose-dependent pharmacodynamic induction of interferon-stimulated gene 15 without significant systemic induction of interferon-alpha or related symptoms, according to recently published data.

“Vesatolimod (GS-9620) is a selective and potent agonist of toll-like receptor 7 (TLR7), a pattern recognition receptor expressed in the endo/lysosomal compartments of plasmacytoid dendritic cells (pDC) and B lymphocytes,” Harry L.A. Janssen, MD, PhD, from the University Health Network, Toronto, and colleagues wrote. “Overall, in virally suppressed patients with [chronic HBV], Vesatolimod was safe and well-tolerated at all doses compared to [placebo].”

In a phase 2 clinical trial, Janssen and colleagues enrolled 162 patients with virally suppressed chronic HBV from 23 international centers. The researchers randomly assigned patients to receive either 1 mg, 2 mg or 4 mg of Vesatolimod (GS-9620, Gilead) for 12 weeks (n = 146) or placebo for 12 weeks (n = 16).

During treatment, one patient treated with 2 mg Vesatolimod, two patients treated with 4 mg, and one patient assigned placebo experienced grade 1 alanine aminotransferase elevation. One patient who received 4 mg Vesatolimod experienced grade 2 ALT elevation. No patients experienced viral breakthrough.

At all dose levels, interferon-stimulated gene (ISG15) increase peaked at 24 hours after treatment initiation and returned to baseline after 1 week. ISG15 levels were dose-dependent and highest among patients treated with 4 mg Vesatolimod (6.6-fold median increased) followed by those treated with 2 mg (3.1-fold median increase) and those treated with 1 mg (1.4-fold median increase).

Multivariate analysis showed that women (OR = 8.77; 95% CI, 2.22-34.48) and patients who received 4 mg vs. 1 mg of Vesatolimod (OR = 36.15; 95% CI, 8.934-146.29) had higher ISG15 responses.

While no patient demonstrated significant serum interferon alpha expression during the study, the researchers also observed no significant HBV surface antigen loss or seroconversion during the study.

Five patients discontinued therapy due to withdrawal of consent (n = 1), protocol violation (n = 1) or adverse event (n = 3). Four patients had treatment-emergent serious adverse events, including two patients who inadvertently received an overdose during treatment, one patient who developed cataract unrelated to treatment, and one patient who developed cholecystitis related to treatment. Overall, patients treated with Vesatolimod and those who received placebo had comparable rates of treatment-emergent adverse events (69% vs. 69%). – by Talitha Bennett

Disclosure: Janssen reports financial connections with AbbVie, BMS, Gilead, Janssen, Medimmune, MSD, Novartis, Roche and Tekmira. Please see the full study for the other authors’ relevant financial disclosures.