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EFFICACY AND SAFETY RESULTS 48 WEEKS AFTER SWITCHING FROMTENOFOVIR DISOPROXIL FUMARATE (TDF) TO TENOFOVIRALAFENAMIDE (TAF) VS CONTINUED TDF TREATMENT INVIROLOGICALLY-SUPPRESSED PATIENTS WITH CHRONIC HEPATITIS B(CHB)Pietro Lampertico, Maria Buti, Scott Fung, Sang Hoon Ahn, Wan-Long Chuang, WonYoung Tak, Alnoor Ramji, Chi-Yi Chen, Edward Tam, Ho Bae, Xiaoli Ma, John F. Flaherty,Anuj Gaggar, Audrey H. Lau, Becket Feierbach, George Wu, Vithika Suri, ManiSubramanian, Huy N. Trinh, Seung-Kew Yoon, Kosh Agarwal, Young-Suk Lim, Henry L.ChanBackground and Aims:TAF, a novel prodrug of tenofovir (TFV), was recently approved for treatment of CHB. TAF has greater plasma stability, more targeted delivery of TFV to the liver, and reduced circulating levels of TFV compared to TDF at approved doses. 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.Method:In this Phase 3 study (NCT02979613), CHB patients on TDF for≥48 weeks with HBV DNA<LLOQ (local laboratory) for≥12 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. After this, all patients received open-label TAF for an additional 48weeks. The primary efficacy analysis was the proportion of patients with HBV DNA≥20IU/mL at Week 48 based on the modified US FDA-defined Snapshot algorithm; the study was powered to show non-inferiority in efficacy of TAF compared to TDF, with a 4% margin.Key prespecified secondary safety endpoints were assessed sequentially: changes in hip and spine bone mineral density (BMD), and changes in estimated creatinine clearance by Cock-croft-Gault (eGFRCG). Markers of bone turnover and renal tubular function were serially assessed. 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 42 sites in 8 countries. At baseline the groups were similar:median age 52 y (22%≥60 y), 71% male, 82% Asian, 68% HBeAg-negative, and medianALT 23 U/L. Median eGFRCGwas 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 in the Table. TAF demonstrated non-inferior efficacy to TDF with a similar rate (0.4%) having HBV DNA≥20 IU/mL at Week48, (difference in proportions: 0.0%, 95% CI, -1.9% to 2.0%). TAF treatment resulted in increases in hip/spine BMD with less impact on bone turnover makers; switching from TDF to TAF also resulted in increased eGFRCG and decreases in markers of tubular function. Rates of ≥Grade 2 adverse events (AEs) and serious AEs were low and similar between groups. No viral resistance was observed in the 3/243 (1.2%) and 2/245 (0.8%) TAF andTDF patients, respectively, who qualified for testing.Conclusion: Virologically-suppressed CHB patients who were switched to TAF demonstrated non inferior efficacy to continued TDF with improved bone and renal safety |
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