China-based Hengrui Pharmaceuticals has initiated a Phase III clinical trial for HRS‑5635, making it the world's first siRNA therapy for chronic hepatitis B (CHB) to advance to this late‑stage development. The randomised, double‑blind, placebo‑controlled study aims to enrol 540 patients who are HBeAg‑negative and have been pre‑treated with nucleos(t)ide analogues. The primary endpoint is the proportion of patients maintaining hepatitis B virus (HBV) DNA suppression and HBeAg negativity 24 weeks after stopping all HBV therapy, a key measure of functional cure.

Early‑phase data underpinning the trial showed a significant reduction in HBeAg levels. Patients receiving HRS‑5635 every four weeks achieved a 1.615 to 1.886 log10 IU/mL decrease, starkly contrasting with the 0.009 log10 IU/mL reduction observed in the placebo group. According to industry databases, HRS‑5635 is currently the only HBV siRNA candidate in Phase III globally, positioning Hengrui at the forefront of this novel therapeutic approach.

PharmCube's NextBiopharm® database lists 13 other clinical-stage siRNA candidates for CHB, including an Alnylam-originated asset which, while it is currently in Phase II for CHB, it already entered late-stage for viral hepatitis. Click here to request a free trial for NextBiopharm®.