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

GS-US-320-0110, GS-US-320-0108 Investigators

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)672-681
Number of pages10
JournalJournal of Hepatology
Volume68
Issue number4
DOIs
Publication statusPublished - 2018 Apr

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Tenofovir
Virus Diseases
Hepatitis B virus
Hepatitis B e Antigens
Chronic Hepatitis B
Safety
Therapeutics
Alanine Transaminase
Kidney
Bone and Bones
GS-7340

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

GS-US-320-0110 ; GS-US-320-0108 Investigators. / 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. In: Journal of Hepatology. 2018 ; Vol. 68, No. 4. pp. 672-681.
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title = "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.",
author = "GS-US-320-0110 and {GS-US-320-0108 Investigators} and Kosh Agarwal and Maurizia Brunetto and Seto, {Wai Kay} and Lim, {Young Suk} and Scott Fung and Patrick Marcellin and Ahn, {Sang Hoon} and Namiki Izumi and Chuang, {Wan–Long L.} and Ho Bae and Manoj Sharma and Janssen, {Harry L.A.} and Pan, {Calvin Q.} and {\cC}elen, {Mustafa Kemal} and Norihiro Furusyo and Dr Shalimar and Yoon, {Ki Tae} and Huy Trinh and Flaherty, {John F.} and Anuj Gaggar and Lau, {Audrey H.} and Cathcart, {Andrea L.} and Lanjia Lin and Neeru Bhardwaj and Vithika Suri and {Mani Subramanian}, G. and Gane, {Edward J.} and Maria Buti and Chan, {Henry L.Y.}",
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language = "English",
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96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. / GS-US-320-0110; GS-US-320-0108 Investigators.

In: Journal of Hepatology, Vol. 68, No. 4, 04.2018, p. 672-681.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection

AU - GS-US-320-0110

AU - GS-US-320-0108 Investigators

AU - Agarwal, Kosh

AU - Brunetto, Maurizia

AU - Seto, Wai Kay

AU - Lim, Young Suk

AU - Fung, Scott

AU - Marcellin, Patrick

AU - Ahn, Sang Hoon

AU - Izumi, Namiki

AU - Chuang, Wan–Long L.

AU - Bae, Ho

AU - Sharma, Manoj

AU - Janssen, Harry L.A.

AU - Pan, Calvin Q.

AU - Çelen, Mustafa Kemal

AU - Furusyo, Norihiro

AU - Shalimar, Dr

AU - Yoon, Ki Tae

AU - Trinh, Huy

AU - Flaherty, John F.

AU - Gaggar, Anuj

AU - Lau, Audrey H.

AU - Cathcart, Andrea L.

AU - Lin, Lanjia

AU - Bhardwaj, Neeru

AU - Suri, Vithika

AU - Mani Subramanian, G.

AU - Gane, Edward J.

AU - Buti, Maria

AU - Chan, Henry L.Y.

PY - 2018/4

Y1 - 2018/4

N2 - 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.

AB - 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.

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