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Safety and Efficacy of 96 Weeks of Tenofovir Disoproxil Fumarate Therapy in Lamivudine Experienced Patients
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EASL
Reported by Jules Levin
M Manns1, L Jeffers2, G Dalekos3, T Berg4, C Trepo5, S Roberts6, M Prieto7, M Rizzetto8, P Marcellin9, E J Heathcote10, J Sorbel11, J Anderson11, E Mondou11, and F Rousseau11
1Gastroenterology, Hepatology & Endocrinology, Center for Internal Medicine, 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, Charite Universitatsmedizin, 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, 8University of Torino,
Dipartimento di Gastroenterologia, Torino Italy; 9University of Paris, Clichy France; 10University of Toronto, Toronto ONT, Canada; 11Gilead Sciences, Inc., Durham NC
AUTHOR CONCLUSIONS
TDF demonstrated potent and durable antiviral efficacy in both LAM-experienced and LAM-naive patients
- 92% of LAM-experienced patients treated for 96 weeks had HBV DNA <400 copies mL (ITT)
TDF was well tolerated up to 96 weeks in both LAM-experienced and LAM-naive patients
No HBV pol/RT amino acid substitutions associated with TDF resistance were detected through 96 weeks of TDF monotherapy in either LAM-experienced or LAM-naïve patients
Introduction
Tenofovir DF (TDF) is a nucleotide analog and obligate chain terminator
Approved for chronic hepatitis B (CHB) in 2008
Week 48 Phase 3 data1 showed that TDF had superior antiviral efficacy to adefovir dipivoxil (ADV) in studies 102 (HBeAg-negative patients) and 103 (HBeAg-positive patients):
- 93% vs. 63% (HBeAg-negative) and 76% vs. 13% (HBeAg positive) with HBV DNA <400 copies/mL (<69 IU/mL) (ITT)
Week 48 data2 also showed a similar virologic response for TDF-treated patients with prior lamivudine-experience versus lamivudine-naïve patients:
- 88% of lamivudine-experienced versus 86% of lamivudine naïve patients had HBV DNA <400 copies/mL (<69 IU/mL) (ITT)
Week 96 antiviral efficacy data demonstrates durable and potent activity in both HBeAg-negative and HBeAg-positive patients:
- 91% of HBeAg-negative3 and 78% of HBeAg-positive4 patients had HBV DNA <400 copies/mL (<69 IU/mL) (ITT)
Objective
To evaluate the response to 96 weeks (2 years) of TDF treatment in the subset of lamivudine-experienced compared to lamivudine-naïve patients with chronic hepatitis B enrolled in the phase 3 studies 102 and 103
Endpoints
· HBV DNA <400 copies/mL (<69 IU/mL) (tested at Week 96)
· HBV DNA over time
· ALT over time
· Safety and tolerability
· Resistance
Resistance Surveillance Results
No HBV pol/RT amino acid substitutions associated with TDF resistance were detected through 96 weeks of TDF monotherapy in either LAM-experienced or LAM-naïve patients5
References
1. Marcellin P, Heathcote J, Buti M et al Tenofovir Disoproxil Fumarate versus Adefovir Dipivoxil for Chronic Hepatitis B. NEJM 2008, Vol 359, pg 2442-2455.
2. Manns M, Jeffers L, Dalekos G et al. The Antiviral Response To Tenofovir Disoproxil Fumarate (TDF) is Comparable in Lamivudine (LAM)-Naïve and LAM-Experienced Subjects Treated for Chronic Hepatitis B (CHB) presented at EASL 2008 (#1587).
3. Marcellin P, Buti M, Krastev Z et al . Two Year Tenofovir Disoproxil Fumarate (TDF) Treatment and Adefovir Dipivoxil (ADV) Switch Data in HBeAg-Negative Patients with Chronic Hepatitis B (Study 102) presented at AASLD 2008 (#146).
4. Heathcote J, Gane E, DeMan R et al. Two Year Tenofovir Disoproxil Fumarate (TDF) Treatment and Adefovir Dipivoxil (ADV) Switch Data in HBeAg-Positve Patients with Chronic Hepatitis B (Study 103) presented at AASLD 2008 (#158).
5. Snow-Lampart A, Chappell B, Curtis M et al Week 96 Resistance Surveillance for HBeAg Positive and Negative Subjects with Chronic HBV Infection Randomized to Receive Tenofovir DF 300 mg QD presented at AASLD 2008 (Poster 977)
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