IDDF2019-ABS-0169 A phase 3 study comparing switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) with continued TDF treatment in virologically-suppressed patients with chronic hepatitis B (CHB): week 48 efficacy and safety results. (June 2019) - Lik Yuen Chan, Henry
Abstract : Background: TAF has shown efficacy non-inferior to TDF with improved renal and bone safety in viremic CHB patients at Weeks 48 and 96. We evaluated efficacy and safety in stable, virally-suppressed patients who were switched from TDF to TAF vs. continued TDF for an additional year. Methods: CHB patients on TDF for ³48 weeks with HBV DNA <LLOQ for ³12 weeks and <20 IU/mL at screening were randomized (1:1) to TAF 25 mg QD or TDF 300 mg QD, each with matching placebo, and treated for 48 weeks. All patients then received open-label TAF for an additional 48 weeks. The primary efficacy analysis was the proportion of patients with HBV DNA ³20 IU/mL at Week 48. Key prespecified secondary safety endpoints were changes in hip and spine bone mineral density (BMD), estimated creatinine clearance by Cockcroft-Gault (eGFRCG ), and markers of bone turnover and renal tubular function. Viral resistance was evaluated by population sequencing those patients who experienced virologic breakthrough or viremia at the time of discontinuation. Results: 488 patients were randomized and treated. At baseline the groups were similar: median age 52 y, 71% male, 82% Asian, 68% HBeAg-negative, median ALT 23 U/L, median eGFRCG 90.5 mL/min; 45% and 50% had low BMD by T scores at hip and spine, respectively. Median (Q1, Q3) duration of prior TDF was 222 (145, 305) weeks. Key efficacy/safety results are summarized (table 1 ). TAF demonstrated non-inferior efficacy to TDF with a similar rate (0.4%) of having HBV DNA ³20 IU/mL at Week 48. TAF resulted in hip/spine BMD increases with less impact on bone turnover makers; switching from TDF to TAF resulted in eGFRCG increases and decreased tubular function markers. Rates of ³Grade 2 adverse events (AEs) and serious AEs were low and similar between groups. No viral resistance was observed. Conclusions: Virologically-suppressed CHB patients who were switched to TAF demonstrated noninferior efficacy to continued TDF with improved bone and renal safety.