Eight‐year efficacy and safety of tenofovir alafenamide for treatment of chronic hepatitis B virus infection: Final results from two randomised phase 3 trials

• Published in: Alimentary pharmacology & therapeutics Vol. 60; no. 11-12; pp. 1573 - 1586
• Main Authors: Buti, Maria, Lim, Young‐Suk, Chan, Henry Lik Yuen, Agarwal, Kosh, Marcellin, Patrick, Brunetto, Maurizia R., Chuang, Wan‐Long, Janssen, Harry L. A., Fung, Scott K., Izumi, Namiki, Jablkowski, Maciej S., Abdurakhmanov, Dzhamal, Abramov, Frida, Wang, Hongyuan, Botros, Irina, Yee, Leland J., Mateo, Roberto, Flaherty, John F., Osinusi, Anu, Pan, Calvin Q., Shalimar, X., Seto, Wai‐Kay, Gane, Edward J.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2024; John Wiley and Sons Inc
• Subjects: Adenine - adverse effects; Adenine - analogs & derivatives; Adenine - therapeutic use; Adult; Alanine - therapeutic use; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Bone mineral density; Chronic infection; Clinical trials; Double-Blind Method; Drug Resistance, Viral; Failure analysis; Female; Fibrosis; Glomerular filtration rate; Hepatitis B; Hepatitis B e antigen; Hepatitis B e Antigens - blood; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatitis B, Chronic - drug therapy; Hip; Humans; Male; Middle Aged; Original; Phenotyping; RNA-directed DNA polymerase; Tenofovir; Tenofovir - analogs & derivatives; Tenofovir - therapeutic use; Tenofovir in Chronic Hbv Infection; Treatment Outcome
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.18278

Summary Background In two phase 3 studies, tenofovir alafenamide (TAF) showed non‐inferior efficacy versus tenofovir disoproxil fumarate (TDF), with more favourable renal and bone safety in patients with chronic hepatitis B (CHB). Aims Here, we report the studies' final 8‐year results. Methods CHB patients (hepatitis B e antigen [HBeAg]‐negative and HBeAg‐positive) were randomised (2:1) to double‐blind TAF 25 mg/day or TDF 300 mg/day for up to 3 years, followed by open‐label (OL) TAF through year 8. Virological, biochemical, serological and fibrosis responses, and safety, including bone and renal parameters, were evaluated. Resistance to TAF was assessed annually by deep sequencing of polymerase/reverse transcriptase and by phenotyping. Results Among 1298 patients randomised to double‐blind TAF (n = 866) or double‐blind TDF (n = 432), 775 in the TAF group and 382 in the TDF group received OL TAF, including 180 and 202 who switched from TDF to TAF at year 2 (TDF2y → TAF6y) or year 3 (TDF3y → TAF5y), respectively. At year 8, among patients in the TAF8y, TDF2y → TAF6y and TDF3y → TAF5y groups, 69%, 66% and 73% (missing‐equals‐failure analysis) and 95%, 94% and 97% (missing‐equals‐excluded) of patients, respectively, achieved HBV DNA <29 IU/mL. Estimated glomerular filtration rate (Cockcroft‐Gault method; eGFRCG) and hip/spine bone mineral density (BMD) remained stable in patients receiving double‐blind/OL TAF, with only small declines at year 8. Decreases in eGFRCG and hip/spine BMD observed during double‐blind TDF improved after switching to OL TAF. No patients developed resistance to TAF. Conclusion Long‐term TAF treatment exhibited favourable safety and tolerability with high rates of viral suppression and no development of resistance. ClinicalTrials.gov numbers NCT01940341 and NCT01940471. In patients with CHB, long‐term treatment with TAF, or with TDF followed by TAF, exhibited favourable safety and tolerability with high rates of viral suppression. No resistance to TAF was detected.