Conference Reports for NATAP

EASL 43rd Annual Meeting of the European Association For The Study Of The Liver Milan, Italy April 23-27, 2008 Back

The Antiviral Response To Tenofovir Disoproxil Fumarate (TDF) is Comparable in Lamivudine (LAM)-NaIve and LAM-Experienced Subjects Treated for Chronic Hepatitis B (CHB)       Reported by Jules Levin 43rd Annual Meeting of the European Association for the Study of the Liver April 23-27, 2008 Milan, Italy   M Manns,1 L Jeffers,2 G Dalekos,3 T Berg,4 C Trepo,5 S Roberts,6 M Prieto,7 M Rizzetto,8 J Sorbel,9 J Anderson,9 E Mondou, 9 J Quinn,9 and F Rousseau9   1Medical School of Hannover, Hannover, Germany; 2University of Miami School of Medicine Center for Liver Diseases, Miami FL; 3University of Thessaly Medical School Academic Liver Unit, Larissa Greece; 4Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, CharitŽ UniversitŠtsmedizin, Berlin; 5Hopital de Hotel Dieu, Service d' Hepatogastro enterologie, Lyon France; 6Alfred Hospital, Dept of Gastroenterology, Melbourne, Australia; 7Hospital La Fe, Servicio de Medicina Digestiva, Valencia Spain, 8 University of Torino, Dipartimento di Gastroenterologia, Torino Italy, 9Gilead Sciences, Inc., Durham NC USA   AUTHOR CONCLUSIONS   · Tenofovir DF demonstrated potent and consistent antiviral efficacy in both LAM Exp and LAM Naive patients · No mutations associated with tenofovir DF resistance were observed in either LAM Exp or LAM Naive patients · Tenofovir DF was well tolerated in both LAM Exp and LAM NaIve patients   INTRODUCTION · Based on data from the Phase 3 studies, GS-174-0102 (HBeAg negative) and GS-174-0103 (HBeAg positive), tenofovir DF showed superior efficacy to adefovir dipivoxil - At Week 48, 76% of HBeAg+ patients and 93% of HBeAg- patients receiving tenofovir DF had HBV DNA <400 c/mL (69 IU/mL) · Both lamivudine naIve (<12 weeks treatment) and lamivudine-experienced patients were enrolled into these studies   OBJECTIVE · To evaluate the Week 48 response to tenofovir DF in the subset of lamivudine-experienced (LAM Exp) compared to lamivudine-naIve (LAM NaIve) patients enrolled in these phase 3 studies   ENDPOINTS · Proportion of patients with HBV DNA <400 c/mL (69 IU/mL) · Mean HBV DNA change from baseline · Proportion of patients with normal ALT · Safety and tolerability   METHODS Key eligibility criteria for Studies 102 (HBeAg-) and 103 (HBeAg+) · Age 18-69 years · Compensated liver disease · HBV DNA > 105 c/mL (HBeAg-) or HBV DNA > 106 c/mL (HBeAg+) · ALT > ULN < 10xULN (HBeAg-) or ALT > 2xULN <10xULN (HBeAg+) · Knodell Necroinflammatory score ≥ 3 · HIV, HDV, HCV negative   Assessments · Liver biopsies pre-treatment and between Week 44 and 48 · HBV DNA and Laboratory analyses (serum chemistry, hematology, and urinalysis) every 4 weeks · HBeAg and HBsAg every 12 weeks · HBV DNA measured using the Roche COBAS TaqMan assay (LLOQ=169 c/mL or 29 IU/mL) · Resistance surveillance performed at baseline for all patients and Week 48 for all viremic patients (≥ 400 c/mL or 69 IU/mL) · Study 102 actively enrolled both LAM experienced and LAM-naIve patients · Study 103 enrolled 8 LAM experienced patients despite LAM-naIve inclusion criteria Resistance Surveillance   · No resistance to tenofovir DF was detected at Week 48 in any subject · Across both pivotal studies 39/426 subjects had HBV DNA > 400 c/mL (69 IU/mL) at Week 48, which included 4 patients with LAM experience · No LAM experienced or naIve patient had genotypic changes associated with resistance to tenofovir