PRINCETON, N.J. -- Bristol-Myers Squibb Company announced data from a cohort of nucleoside-naive HBeAg-negative chronic hepatitis B patients (ETV-027/901, n=99). These data showed that patients who experienced recurrent levels of hepatitis B virus in the blood after interruption of treatment with BARACLUDE® (entecavir) achieved viral suppression and liver enzyme (ALT) normalization when re-treated for 48 weeks with BARACLUDE. The study results were presented at the 42nd Annual Meeting of the European Association for the Study of Liver Diseases (EASL) in Barcelona, Spain.
In this cohort, 93 percent of patients who were re-treated with BARACLUDE had undetectable viral load -- the level of the hepatitis B virus in the blood -- (HBV DNA <300 copies/mL, measured by a common assay -- polymerase chain reaction or PCR) and 83 percent achieved liver enzyme normalization (ALT less than or equal to 1xULN) after 48 weeks of therapy.
"This study showed that when treated again with BARACLUDE for 48 weeks, patients achieved responses similar to those seen prior to treatment interruption, with safety results consistent with previously reported experience," said Hakan Senturk, MD, of the Ist. Univ. Cerrahpasa Tip Fak, Istanbul, Turkey.
No deaths or treatment discontinuations due to adverse events were reported in this cohort. The most common adverse events occurring in greater than 10 percent of patients were abdominal pain, fatigue, upper respiratory tract infection, nasopharyngitis, increased ALT, arthralgia, and headache.
Nucleoside-Naive HBeAg-Negative BARACLUDE® Re-Treatment Cohort
This analysis evaluated BARACLUDE® (entecavir) in nucleoside-naive chronic HBeAg-negative patients who discontinued study therapy in ETV-027, and subsequently restarted treatment in rollover study ETV-901, with a greater than 60-day gap between end of treatment in study ETV-027 and start of treatment in study ETV-901.
-- ETV-027 compared 0.5 mg of BARACLUDE vs. 100 mg of lamivudine in nucleoside-naive chronic HBeAg-negative chronic hepatitis B patients.
-- Rollover study ETV-901 was established as an open-label, follow-up protocol for patients in phase II and III studies of BARACLUDE.
-- Due to ongoing blinding of study ETV-027, most patients retreated in ETV-901 initially received a combination of 1 mg of BARACLUDE plus 100 mg of lamivudine, and were subsequently switched to 1 mg of BARACLUDE monotherapy.
The analysis cohort was defined regardless of treatment response at the end of dosing in study ETV-027, and independent of virologic or ALT measurements at the start of dosing in study ETV-901. During off-treatment follow-up, the majority of patients had recurrent levels of hepatitis B virus in the blood (viremia) and increases in ALT.
Data Results
At the end of dosing for study ETV-027:
-- 94 percent (n=93/99) of the re-treatment cohort had undetectable viral load
-- 78 percent (n=77/99) had ALT normalization
At entry into ETV-901:
-- Four percent (n=4/99) of patients had undetectable viral load
-- Eight percent (n=8/97) of patients had ALT normalization
Following re-treatment in study ETV-901:
-- 93 percent (n=82/88) of patients had undetectable viral load (HBV DNA <300 copies/mL) by week 48 of re-treatment with BARACLUDE
-- 83 percent (n=79/95) of patients had ALT normalization (ALT less than or equal to 1 times the upper limit of normal) by week 48 of re-treatment BARACLUDE
Adverse events in study ETV-027/901 re-treatment cohort:
-- 67 percent (n=66/99) of patients experienced an adverse event. The most common adverse events occurring in greater than 10 percent of patients were abdominal pain, fatigue, upper respiratory tract infection, nasopharyngitis, increased ALT, arthralgia, and headache.
-- There were no deaths or treatment discontinuations due to adverse events.
-- Nine percent (n=9/99) of patients experienced a serious adverse event. Serious adverse events included ALT elevation or hepatitis exacerbation (4), bilirubin elevation (1), inguinal hernia (1), sialoadenitis (1), thrombocytopenic purpura (1), groin pain (1), macular edema (1), urinary incontinence (1) and cholelithiasis (1). Two of these events, hepatitis exacerbation (1) and thrombocytopenia (1), were considered possibly related to treatment by the investigator.
-- Five percent (n=5/99) of patients experienced an ALT flare on treatment (ALT > 2 times baseline and >10 times the upper level of normal)
Source: Bristol-Myers Squibb