Efficacy and Safety of Tenofovir Alafenamide in Chronic Hepatitis B Infection

29 Jun, 20

Introduction

Tenofovir alafenamide (TAF) is an orally bioavailable new prodrug of tenofovir designed to have a better plasma stability than tenofovir disoproxil fumarate (TDF), resulting in more efficient delivery of tenofovir to hepatocytes. Two large ongoing, double-blind, randomized phase III trials are being conducted to compare the efficacy and safety of TAF and TDF in treatment-na?ve and treatment-experienced patients with chronic hepatitis B virus (HBV) infection. The results demonstrated the non-inferiority of TAF to TDF in efficacy with improved renal and bone safety after 48 weeks.

Aim

To compare the efficacy and safety of TAF and TDF after 96 weeks of treatment in patients with chronic hepatitis B (CHB) infection.

Method

Study Design

Randomized, double-blind, active-controlled, international phase 3 trials

Treatment Strategy

HBeAg-negative and HBeAg-positive patients, enrolled in these two trials, were randomized 2:1 to receive treatment with 25 mg TAF or 300 mg TDF once daily in a double-blinded manner
The cohort underwent laboratory assessments
Bone mineral density was also evaluated after every 24 weeks

Endpoints

Proportion of patients with plasma HBV DNA <29 IU/ml
Proportion of patients with hepatitis B surface antigen (HBsAg) loss and seroconversion to anti-HBs
Proportion of patients with normalization of alanine aminotransferase (ALT) levels
Adverse events

Results

Out of the 873 HBsAg-positive patients originally recruited in 1 trial (581 TAF and 292 TDF), 91% completed this study (530 TAF and 262 TDF)
Out of the 425 HBsAg-negative patients originally enrolled in the 2^nd trial (285 TAF and 140 TDF), 93% completed this study (266 TAF and 129 TDF)
The proportion of patients attaining HBV DNA levels <29 IU/ml at week 96 were similar in patients receiving TAF and TDF as shown in table 1.

Table 1. Viral suppression in TAF and TDF groups

	TAF group	TDF group	Adjusted difference	p values
HBsAg-positive patients	73%	75%	-2.2%	0.47
HBsAg-negative patients	90%	91%	-0.6%	0.84

There were significantly higher proportions of patients with normalized ALT levels at week 96 of treatment in TAF group in both the studies
The rate of HBsAg loss at week 96 was 1% in both the groups
HBsAg seroconversion was 1% in TAF group as compared to 0 in the TDF group
The pooled safety analyses are presented in table 2.

Table 2. Pooled safety analyses

	TAF group	TDF group	P value
Mean % decrease in hip BMD at week 96	-0.33%	-2.51%	<0.001
Mean % decrease in spine BMD at week 96	-0.75%	-2.57%	<0.001
Median change in estimated glomerular filtration rate	-1.2 mg/dl	-4.8 mg/dl	<0.001

None of the patients reported any serious renal adverse event leading to treatment discontinuation in both the groups

Conclusion

After 2 years of treatment, tenofovir alafenamide (TAF) was as effective as tenofovir disoproxil fumarate (TDF) in suppressing hepatitis B virus (HBV) replication with no documented virologic resistance
Treatment for 2 years with TAF was associated with a better renal and bone safety profile as compared to TDF.

J Hepatol. 2018 Jan;68(4):672-81. Doi: 10.1016/j.jhep.2017.11.039.