96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection.

Abstract

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.

• Authors: Kosh Agarwal, Maurizia Brunetto, Wai Kay Seto, Young-Suk Lim, Scott Fung, Patrick Marcellin, Sang Hoon Ahn, Namiki Izumi, Wan-Long Chuang, Ho Bae, Manoj Sharma, Harry L A Janssen, Calvin Q Pan, Mustafa Kemal Çelen, Norihiro Furusyo, Dr Shalimar, Ki Tae Yoon, Huy Trinh, John F Flaherty, Anuj Gaggar, Audrey H Lau, Andrea L Cathcart, Lanjia Lin, Neeru Bhardwaj, Vithika Suri, G Mani Subramanian, Edward J Gane, Maria Buti, Henry L Y Chan, GS-US-320-0110, GS-US-320-0108 Investigators
• Journal: Journal of hepatology (J Hepatol) Vol. 68 Issue 4 Pg. 672-681 (04 2018) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 29756595 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• DNA, Viral
• Hepatitis B e Antigens
• Tenofovir
• Alanine Transaminase
• tenofovir alafenamide
• Adenine
• Alanine

Topics

• Adenine (analogs & derivatives, therapeutic use)
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Alanine
• Alanine Transaminase (blood)
• Bone Density (drug effects)
• DNA, Viral (analysis)
• Double-Blind Method
• Drug Resistance, Viral
• Female
• Glomerular Filtration Rate (drug effects)
• Hepatitis B (drug therapy, virology)
• Hepatitis B e Antigens (analysis)
• Humans
• Male
• Middle Aged
• Tenofovir (therapeutic use)
• Young Adult