Hepatitis B virus (HBV) is suppressed in vitro by selgantolimod (GS-9688), a toll-like receptor 8 (TLR8) agonist. In Phase 2 research, researchers assessed the safety and effectiveness of weekly selgantolimod treatment in chronic HBV patients receiving oral antiviral therapy.

For 24 weeks, while continuing oral antivirals, 48 patients were randomized to receive oral selgantolimod 3 mg, 1.5 mg, or placebo (2:2:1) once a week. The patients were divided into 2 groups (hepatitis B e antigen [HBeAg]-positive and -negative [n=24 each]). The primary efficacy goal was the percentage of patients with a decrease of ≥1 log10 IU/mL in HBsAg from baseline to week 24. Following therapy, individuals took oral antivirals for an additional 24 weeks.

One HBeAg-negative individual who received 1.5 mg of selgantolimod met the main objective. Only patients receiving selgantolimod (n=39) experienced HBsAg decreases larger than 0.1 log10 IU/mL at weeks 24 (18%, 7/39) and 48 (26%, 10/39) as well as HBsAg loss (5%, 2/39 through 48 weeks) or HBeAg loss (16%, 3/19 through 48 weeks), in contrast to patients receiving placebo (n=9). In those receiving selgantolimod, nausea (46%), upper respiratory tract infection (23%), and vomiting (23%) were the most frequent side effects. The majority of gastrointestinal illnesses were minor and transitory. Selgantolimod produced fast redistribution of several circulating immune cell subsets as well as temporary dose-dependent elevations in serum cytokines such IL-12p40, IFN-γ, and IL-1RA.

Generally safe and well tolerated, oral selgantolimod up to 3 mg once weekly for 24 weeks resulted in serologic alterations associated with progression to lasting cure in 2 patients by week 48.

Reference: journal-of-hepatology.eu/article/S0168-8278(22)03148-8/fulltext