Safety
and Efficacy of 96 Weeks of Tenofovir (Viread) in Chronic Hepatitis B Patients
Previously Treated with Lamivudine (Epivir-HBV) The
U.S. Food and Drug Administration (FDA) approved tenofovir
(Viread) for the treatment
of chronic hepatitis B virus (HBV) infection in August 2008; the drug has
been approved for HIV treatment since 2001. Tenofovir
has previously demonstrated activity against HBV that has developed resistance
to lamivudine (Epivir-HBV). In
a presentation at the 44th Annual Meeting of the European Association for the
Study of the Liver (EASL 2009) last week in Copenhagen, investigators presented
data on tenofovir response at 96 weeks among a subset of participants from studies
102 and 103 who had previously been treated for more than 12 weeks with lamivudine
or the related drug emtricitabine
(Emtriva). In
these pivotal double-blind Phase 3 studies, participants were randomized 2:1 to
receive 300 mg once-daily tenofovir or 10 mg once-daily adefovir
(Hepsera). After 48 weeks, patients with a week 48 biopsy continued on open-label
tenofovir for up to 7 additional years. Study
102 included hepatitis B "e" antigen (HBeAg) negative patients, while
Study 103 included HBeAg positive participants. Across both studies, a total of
426 patients were initially randomized to the tenofovir arm (51 lamivudine-experienced
and 375 lamivudine-naive). HBV
suppression was defined as HBV DNA < 400 copies/mL or 69 IU/mL. Results
49 lamivudine-experienced and 350 lamivudine-naive patients completed 96 weeks
of tenofovir treatment; a majority of lamivudine-experienced patients (n = 41)
were HBeAg negative.
In an intent-to-treat analysis, a similar proportion of patients achieved HBV
suppression at week 96 in the lamivudine-experienced and lamivudine-naive subgroups
(92% vs 84%).
Response rates were also similar in an on-treatment analysis (98% vs 95%, respectively).
91% of lamivudine-experienced and 77% of lamivudine-naive patients had normal
ALT at week 96.
No lamivudine-experienced patients achieved hepatitis B surface antigen (HBsAg)
loss.
No HBV pol/RT amino acid substitutions associated with tenofovir resistance were
detected through 96 weeks of tenofovir monotherapy in lamivudine-experienced patients.
During year 2, no lamivudine-experienced patients experienced serious adverse
events or discontinued therapy due to an adverse event.
5 patients experienced new grade 3-4 laboratory abnormalities; elevated serum
lipase (4%) was the only abnormality occurring in more than 1 patient (n = 2).
While receiving open-label tenofovir for 96 weeks, no lamivudine-experienced patients
had a confirmed decrease in creatinine clearance < 50 mL/min, an increase in
creatinine of > 0.5 mg/dL, or a graded serum creatinine abnormality.
Based
on these findings, the investigators concluded, "The safety, efficacy, and
resistance analysis results for 96 weeks of tenofovir treatment were similar in
lamivudine-experienced and lamivudine-naive chronic HBV patients. Longer follow
up is ongoing." Medizinische
Hochschule Hannover, Hannover, Germany; University of Miami School of Medicine,
Miami, FL; University of Thessaly Medical School, Larissa, Greece, Charité
Universitätsmedizin, Berlin, Germany; Hopital de Hotel Dieu, Lyon, France;
Alfred Hospital, Melbourne, Victoria, Australia; Hospital La Fe, Valencia, Spain;
University of Torino, Torino, Italy; University of Paris, Clichy, France; University
of Toronto, Toronto, Ontario, Canada; Gilead Sciences, Inc., Durham, NC. 4/28/09 Reference
M
Manns, L Jeffers, G Dalekos, and others. Safety
and efficacy of 96 weeks of tenofovir disoproxil fumarate therapy in lamivudine-experienced
patients. 44th Annual Meeting of the European Association for the Study of
the Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009.
EASL
2009 MAIN PAGE
EASL
2009 Conference Coverage
HIV and Hepatitis.com Highlights from EASL 2009
15th
Conference on Retroviruses and Opportunistic Infections (CROI 2009)
Coverage
by HIV and Hepatitis.com - February 8 - 11, 2009, Montreal
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