Tenofovir prodrug for CHB on par with tenofovir disoproxil fumarate

HS-10234, a novel tenofovir prodrug, is well-tolerated and as potent as tenofovir disoproxil fumarate (TDF) in the treatment of patients with chronic hepatitis B (CHB) infection, according to the results of a phase Ib trial.

A total of 36 treatment‐naïve adult patients (77.8 percent male; 33.3 percent hepatitis B e antigen [HBeAg]-negative) with noncirrhotic CHB were divided into three groups (n=12 per group). Within each group, patients were randomized to receive 10, 25, or 40 mg of HS‐10234, or 300 mg of TDF once a day for 28 days.

Mean baseline hepatitis B virus (HBV) DNA levels varied between 6.32 and 7.42 log10 IU/mL and did not significantly differ across the treatment groups. The same was true for pretreatment serum hepatitis B surface antigen (HBsAg) and alanine aminotransferase (ALT) levels.

HS-10234 was safe and well-tolerated. A total of 95 adverse events (AEs) occurred in 27 patients (75 percent) and 42 adverse reactions in 24 (66.7 percent). All events were mild or moderate and nonspecific, and none of the patients experienced nephrotoxicity and serious AEs.

In terms of efficacy, serum HBV DNA after 28 days decreased by −2.70, −2.89, −2.72, and −3.04 log₁₀ IU/mL on 10-, 25-, and 40-mg HS‐10234, and 300-mg TDF, respectively.

HS‐10234 and its metabolite tenofovir demonstrated linear, dose‐proportional pharmacokinetics. The concentrations of active metabolite tenofovir diphosphate in peripheral blood mononuclear cells were about two- to 11‐fold higher, while tenofovir concentrations in plasma were approximately 4.5‐ to 25‐fold lower in patients on HS‐10234 than in those on TDF.