Highlights
- •TAF is a new prodrug of tenofovir developed to treat patients with chronic HBV.
- •A lower dose of TAF can be used because it delivers tenofovir more efficiently to hepatocytes than TDF.
- •At week 48, TAF had non-inferior efficacy to TDF with improved renal and bone safety.
- •Efficacy and safety results at week 96 confirm the 48-week results in both studies.
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: January 16, 2018
Accepted:
November 12,
2017
Received in revised form:
October 13,
2017
Received:
August 3,
2017
Identification
Copyright
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
