Background & Aims: Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF) through more efficient delivery of tenofovir to hepatocytes. In 48-week results from two ongoing, double-blind, randomized phase III trials, TAF was non-inferior to TDF in efficacy with improved renal and bone safety. We report 96-week outcomes for both trials. Methods: In two international trials, patients with chronic HBV infection were randomized 2:1 to receive 25 mg TAF or 300 mg TDF in a double-blinded fashion. One study enrolled HBeAg-positive patients and the other HBeAg-negative patients. We assessed efficacy in each study, and safety in the pooled population. Results: At week 96, the differences in the rates of viral suppression were similar in HBeAg-positive patients receiving TAF and TDF (73% vs. 75%, respectively, adjusted difference −2.2% (95% CI −8.3 to 3.9%; p = 0.47), and in HBeAg-negative patients receiving TAF and TDF (90% vs. 91%, respectively, adjusted difference −0.6% (95% CI −7.0 to 5.8%; p = 0.84). In both studies the proportions of patients with alanine aminotransferase above the upper limit of normal at baseline, who had normal alanine aminotransferase at week 96 of treatment, were significantly higher in patients receiving TAF than in those receiving TDF. In the pooled safety population, patients receiving TAF had significantly smaller decreases in bone mineral density than those receiving TDF in the hip (mean % change −0.33% vs. −2.51%; p <0.001) and lumbar spine (mean % change −0.75% vs. −2.57%; p <0.001), as well as a significantly smaller median change in estimated glomerular filtration rate by Cockcroft-Gault method (−1.2 vs. −4.8 mg/dl; p <0.001). Conclusion: In patients with HBV infection, TAF remained as effective as TDF, with continued improved renal and bone safety, two years after the initiation of treatment. Clinicaltrials.gov number: NCT01940471 and NCT01940341. Lay summary: At week 96 of two ongoing studies comparing the efficacy and safety of tenofovir alafenamide (TAF) to tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B patients, TAF continues to be as effective as TDF with continued improved renal and bone safety. Registration: Clinicaltrials.gov number: NCT01940471 and NCT01940341.
Bibliographical noteFunding Information:
Maurizia Brunetto: Advisory Board – Gilead, Merck, AbbVie, Janssen; Speaker – AbbVie, BMS, Gilead, Janssen, Merck, Roche. Wai Kay Seto: Advisory Board-Gilead, AbbVie, Bristol-Myers Squibb; Speaker’s Bureau-Gilead, AbbVie, Bristol-Myers Squibb, Novartis, AstraZeneca, Alfa Wassermann. Young-Suk Lim: Advisory Board – Bayer, Bristol-Myers Squibb, Gilead; Research – Bayer, Bristol-Myers Squibb, Gilead Sciences, Novartis; Speaker – Bayer, Gilead. Sang Hoon Ahn: Advisory Board – Bristol-Myers Squibb, Gilead, AbbVie, MSD; Research – Bristol-Myers Squibb, Gilead Sciences, Roche. Namiki Izumi: Advisory Board-Gilead; Speaker-Gilead, AbbVie, Shionogi, Otsuka, Bayer, MSD. Wan-Long Chuang: Advisory board–Gilead, AbbVie, BMS, MSD, PharmaEssentia; Speaker–Gilead, AbbVie, BMS, MSD, PharmaEssentia, Roche. Ho Bae: Speaker and research grant for Gilead. Harry L.A. Janssen: Grants – AbbVie, Bristol-Myers Squibb, Gilead Sciences, Innogenetics, Janssen, MedImmune, Medronic, Merck, Roche; Consultant – AbbVie, Benitec, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, Roche, Arbutus. Calvin Q. Pan: Consultant – Gilead, AbbVie; Advisory Board – Gilead, BMS, AbbVie; Research – Gilead, Merck. Employees and stockholders of Gilead Sciences: John F. Flaherty, Anuj Gaggar, Audrey H. Lau, Vithika Suri, Andrea L. Cathcart, Neeru Bhardwaj, Lanjia Lin, and G. Mani Subramanian. Huy Trinh: Research—Gilead, Intercept; Advisory Board and Speaker—Gilead. Edward J. Gane: Advisory Board – AbbVie, ALIOS, Gilead, Janssen, Roche; Speaker—Gilead, AbbVie. Maria Buti: Advisory Board and Speaker – Gilead, MSD, BMS, Janssen, AbbVie. Henry L.Y. Chan: Advisor and speaker for AbbVie, BMS, Gilead and Roche; Advisor for Janssen; Speaker for MSD. No relevant conflicts of interest to disclose: Scott Fung, Patrick Marcellin, Manoj Sharma, Mustafa Kemal Çelen, Norihiro Furusyo, Dr. Shalimar, Ki Tae Yoon.
This study was sponsored by Gilead Sciences . Writing assistance was provided by David McNeel of Gilead Sciences .
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