Selgantolimod well tolerated, induces serologic changes in CHB patients

Treatment with the oral Toll-like receptor 8 (TLR8) agonist selgantolimod once weekly for 24 weeks is well tolerated and generally safe in patients with chronic hepatitis B (CHB) under viral suppression, according to a recent study.

By week 48, use of the TLR8 agonist has resulted in serologic changes associated with progression to durable cure in two individuals.

The researchers randomized 48 patients with CHB into two cohorts (hepatitis B e antigen [HBeAg]-positive and -negative; n=24 each) to receive oral selgantolimod 1.5 mg, 3.5 mg, or placebo (2:2:1) once weekly for 24 weeks while maintaining oral antivirals.

The percentage of patients with a ≥1 log10 IU/ml decline in hepatitis B surface antigen (HBsAg) from baseline to week 24 was the primary efficacy endpoint. Patients continued taking oral antiviral medications for 24 weeks post-treatment.

Only one participant, who was HBeAg-negative and received selgantolimod 1.5 mg, achieved the primary endpoint. In addition, only patients treated with selgantolimod (n=39) attained HBsAg declines >0.1 log₁₀ IU/ml at weeks 24 (18 percent, 7/39) and 48 (26 percent, 10/39), HBsAg loss (5 percent, 2/39 through 48 weeks), or HBeAg loss (16 percent, 3/19 through 48 weeks) relative to those who received placebo (n=9).

Among CHB patients treated with selgantolimod, the most common adverse events were nausea (46 percent), upper respiratory tract infection (23 percent), and vomiting (23 percent). Most gastrointestinal disorders were mild and transient.

In addition, selgantolimod promoted transient dose-dependent increases in serum cytokines, including IL-12p40, IFN-γ, and IL-1RA, as well as rapid redistribution of some circulating immune cell subsets, according to the researchers.