IDDF2024-ABS-0201 Long-term safety profile of tenofovir alafenamide in chronic hepatitis B patients; final 8-year results of 2 phase 3 studies

<h3>Background</h3> In 2 similarly designed double-blind (DB), randomized (2:1), Phase 3 studies (Study 108 in HBeAg-negative [N=425] and Study 110 in HBeAg-positive [N=873] patients), tenofovir alafenamide (TAF) demonstrated non-inferior efficacy with superior renal and bone safety compared to tenofovir disoproxil fumarate (TDF) at week 96. After completing DB treatment, all patients were eligible to receive open-label (OL) TAF through week 384 (year 8). Here, we present the final safety results at year 8. <h3>Methods</h3> In a pooled analysis, treatment-emergent adverse events (AEs), serious AEs (SAEs), discontinuations, and laboratory abnormalities were assessed in patients who received OL TAF. Changes from baseline in estimated GFR (by Cockcroft-Gault; eGFR_CG) and changes in hip and spine bone mineral density (BMD) by dual x-ray absorptiometry (DXA) scans were assessed. <h3>Results</h3> Of 1298 randomized and treated patients, 1157 (89%; 775 TAF; 382 TDF) entered the OL phase. Overall, 974 (75%) participants completed OL study treatment. The overall incidence of patients experiencing AEs was similar among groups (IDDF2024-ABS-0201 Table 1). Rates of Grade 3/4 AEs and AEs leading to discontinuation (D/C) were low and similar among groups. Few Grade 3/4 AEs or SAEs were related to the study drug. Overall, the most common Grade 3/4 lab abnormalities (&gt;2%) were increased amylase (TAF 1.9%, TDF-TAF 2.7%), creatine kinase (TAF 1.4%, TDF-TAF 2.1%), fasting cholesterol (TAF 1.4%, TDF-TAF 2.9%), fasting LDL (TAF 5.9%, TDF-TAF 8.0%), and urine glucose (TAF 5.2%, TDF-TAF 2.7%). After experiencing declines in eGFR_CG and hip/spine BMD with TDF treatment in the DB phase, renal and bone outcomes improved following the switch to OL TAF with minimal change through year 8. Overall, low rates of hepatocellular carcinoma (HCC) were observed over 8 years, with 11 cases occurring in the DB and 10 in the OL phases of the study. <h3>Conclusions</h3> Long-term TAF treatment was safe and well tolerated, with minimal changes in eGFR_CG and BMD occurring over 8 years.