O-030: A Phase 3 Study of Tenofovir Alafenamide Compared with Tenofovir Disoproxil Fumarate in Patients with HBeAg-positive Chronic Hepatitis B

Aims: Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV),is more stable in plasma and enhances delivery of TFV into hepatocyteswhile lowering circulating levels of TFV by approximately 90% comparedto tenofovir disoproxil fumarate (TDF).Methods: In this Phase 3 study, patients with HBeAg-positive chronichepatitis B (CHB) were randomized 2:1 to TAF 25 mg QD or TDF300 mg QD and treated for 96 weeks. After Week 96, patients receiveopen label TAF for 48 weeks. The primary efficacy analysis was thepercent of patients with HBV DNA <29 IU/mL at Week 48. Key secondarysafety endpoints were assessed sequentially: changes in hip andspine bone mineral density (BMD), changes in serum creatinine (sCr),and dipstick proteinuria. Markers of bone formation and resorption,and renal tubular function were also assessed.Results: 873 patients were randomized and treated at 164 sites in19 countries. Baseline characteristics included: mean age 38 years,83% males, 82% Asians; 47% had HBV DNA ≥ 8 log10 IU/mL, and26% were treated previously with nucleos(t)ides. At Week 48, TAFwas non-inferior in efficacy to TDF with virologic response rates of63.9% with TAF and 66.8% with TDF. A greater percentage of patientstreated with TAF achieved normalization of serum ALT values.Patients on TAF experienced significantly less declines in hip and spineBMD, and a smaller increase in sCr than TDF; eGFRCG, and renaltubular markers also changed less with TAF. No viral resistance wasobserved in 22/581 (3.8%) and 11/292 (3.8%) of TAF and TDF patients,respectively, who qualified for testing.Conclusions: Compared to TDF 300 mg, the efficacy of TAF 25 mgin patients with HBeAg-positive CHB was noninferior. Safety wasalso improved, with less change in bone and renal parameters.