IDDF2024-ABS-0195 Long-term efficacy of tenofovir alafenamide in HBeAg-positive and -negative chronic hepatitis B patients treated for up to 8 years in 2 phase 3 studies

Background

In 2 similarly designed double-blind (DB), randomized (2:1), Phase 3 studies (Study 108 in HBeAg-negative patients [N=425] and Study 110 in HBeAg-positive patients [N=873]), tenofovir alafenamide (TAF) demonstrated non-inferior efficacy relative to tenofovir disoproxil fumarate (TDF) in the blinded assessments. After completing up to 3 years (yr) of DB treatment, all patients were eligible to receive open-label (OL) TAF through week 384 (yr 8). Here, we present the final 8-yr results.

Methods

Efficacy was assessed for each study by missing equals excluded (M=E) approach of the full analysis set and included serial assessments for viral suppression (HBV DNA < 29 IU/mL), ALT normalization by 2018 AASLD criteria, serologic responses, and fibrosis change by serum FibroTest. Resistance analyses, including deep sequencing of HBV pol/RT (at baseline and annually), for those with virologic breakthrough/blip, persistent viremia, or treatment discontinuation with viremia were performed, as was phenotyping of qualifying samples.

Results

Of 1298 randomized and treated patients, 1157 (89%; 775 TAF; 382 TDF) entered the OL phase, including 180 and 202 TDF-treated patients who began OL TAF at week 96 (TDF-OL TAF 6 yr) or week 144 (TDF-OL TAF 5 yr) based on the timing of a protocol amendment. Overall, 974 (75%) participants completed OL study treatment. The most common reasons for discontinuation were withdrawal of consent, loss to follow-up, or investigator discretion. Similar high rates of virologic suppression and ALT normalization were achieved and maintained over 8 yr in all treatment groups (IDDF2024-ABS-0195 Table 1). Sequence/phenotyping analysis through 6 yr showed no resistance to TAF; resistance analyses at yr 8 are ongoing.

Conclusions

After 8 yr of treatment with TAF or up to 6 yr after switching from TDF, virologic suppression rates remained high across all groups; up to 33% achieved HBeAg/HBeAb seroconversion, while HBsAg loss was low (≤5%).