Bristol-Myers Squibb Company today announced new data from the E.A.R.L.Y. study (ETV-079), in which treatment of antiviral-naïve adult chronic hepatitis B patients with BARACLUDE® (entecavir) resulted in greater long-term viral load reduction than adefovir at 96 weeks -- consistent with earlier 12-week results (primary endpoint).

Milan, Italy (PRWEB) April 26, 2008 -- Bristol-Myers Squibb Company (NYSE:BMY) today announced new data from the E.A.R.L.Y. study (ETV-079), in which treatment of antiviral-naïve adult chronic hepatitis B patients with BARACLUDE® (entecavir) resulted in greater long-term viral load reduction than adefovir at 96 weeks — consistent with earlier 12-week results (primary endpoint). Suppression of viral load to undetectable levels is a measure of antiviral treatment response and is an important goal of chronic hepatitis B treatment. These data were presented today in Milan, Italy, at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL).

The E.A.R.L.Y. study is an open-label, randomized, viral kinetics study of 69 antiviral-naïve chronic hepatitis B e-antigen (HBeAg) positive patients, comparing the antiviral activity of BARACLUDE and adefovir. All patients in this study had a high viral load at study entry.¹ Of the 49 patients who remained in the study at 96 weeks, 79 percent (n=23/29) of BARACLUDE-treated patients and 50 percent (n=10/20) of adefovir-treated patients achieved undetectable viral load.² The mean reduction in viral load from baseline in patients treated with BARACLUDE was -7.82 log10 copies/mL and was -5.96 log10 copies/mL in patients treated with adefovir at week 96.

“BARACLUDE maintains considerable antiviral efficacy through two years of treatment in this analysis,” said Nancy Leung, M.D., of the Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China. “This is important information for health care providers to consider when evaluating initial treatment options to suppress viral load in antiviral-naive chronic hepatitis B patients.”

¹Patients were required to have a screening viral load of greater than or equal to 108 copies/mL at study entry.
²In this study, undetectable viral load was defined as HBV DNA less than 300 copies/mL, measured by PCR assay.

The safety profile was comparable between the treatment groups through 96 weeks. Three percent of patients receiving BARACLUDE® (entecavir) (n=1) and 12 percent of patients receiving adefovir (n=5) experienced a serious adverse event. No deaths were observed in either treatment group. The most common adverse events occurring in greater than 10 percent of patients in either treatment group were headache, nasopharyngitis, upper respiratory tract infection, influenza, pyrexia, urinary tract infection, cough, back pain, and diarrhea.

Data Results
By week 96, 22 of the 69 enrolled patients had discontinued the study. Of these, two patients receiving adefovir discontinued due to investigator-determined lack of treatment efficacy between the beginning of year two dosing and the 96-week analysis. The 96-week data reported below represent the results of the 49 patients who entered year two dosing (29 BARACLUDE-treated patients and 20 adefovir-treated patients), using the non-completer = failure (NC=F) method of analysis.

Week 96

• BARACLUDE-treated patients achieved a mean change in viral load of -7.82 log10 copies/mL from baseline, and adefovir-treated patients achieved a mean change of -5.96 log10 copies/mL.

1     79 percent (n=23/29) of BARACLUDE-treated patients and 50 percent (n=10/20) of adefovir-treated patients had undetectable viral load (HBV DNA less than 300 copies/mL, measured by the polymerase chain reaction or PCR assay).

2     No BARACLUDE-treated patient (n=0/29) and 35 percent (n=7/20) of adefovir-treated patients had viral load greater than or equal to 105 copies/mL.

3     97 percent (n=28/29) of BARACLUDE patients achieved ALT normalization (ALT of less than or equal one time the upper limit of normal) compared with 85 percent (n=17/20) of adefovir-treated patients.

4     24 percent (n=7/29) BARACLUDE-treated patients achieved HBe seroconversion compared with 25 percent (n=5/20) adefovir-treated patients.

5     Six BARACLUDE® (entecavir)-treated patients and 16 adefovir-treated patients discontinued therapy prior to week 96.

• No BARACLUDE-treated patients and one adefovir-treated patient discontinued due to adverse events.

1     No BARACLUDE-treated patients and six adefovir-treated patients discontinued due to investigator-determined treatment failure or lack of efficacy.

2     Three BARACLUDE-treated patients and four adefovir-treated patients met the treatment response criteria at 52 weeks and entered a 24- or 48-week off-treatment follow-up monitoring phase.

3     Two BARACLUDE-treated patients and one adefovir-treated patient were lost to follow-up, one BARACLUDE-treated patient was non-compliant, two adefovir-treated patients withdrew consent, one adefovir-treated patient became pregnant, and one adefovir-randomized patient was treated with BARACLUDE.

Week 12 (primary endpoint)

• BARACLUDE-treated patients achieved a mean change in viral load of -6.23 log10 copies/mL from baseline, compared to adefovir-treated patients who achieved a mean change of -4.42 log10 copies/mL (p < 0.0001).
• 12 percent of BARACLUDE-treated patients and 9 percent of adefovir-treated patients had undetectable viral load (HBV DNA <300 copies/mL).

Additional Cumulative Safety Results of the E.A.R.L.Y. Study at 96 Weeks

• 83 percent of patients in the BARACLUDE arm (n=30) and 82 percent of patients in the adefovir arm (n=27) experienced any adverse event.
• Eight percent of patients receiving BARACLUDE (n=3) and 15 percent of patients receiving adefovir (n=5) experienced any Grade 3-4 adverse event.
• Three percent of patients receiving BARACLUDE (n=1) and 12 percent of patients receiving adefovir (n=5) experienced a serious adverse event.
• No deaths were observed in either treatment group.
• No patients in the BARACLUDE arm and one patient in the adefovir arm experienced an ALT flare (defined as ALT greater than two times baseline and greater than 10 times the upper limit of normal).

About the Study

The E.A.R.L.Y. study (ETV-079) is a randomized, open-label, comparative viral kinetics study of antiviral-naïve chronic HBeAg-positive patients evaluating antiviral activity as measured by mean reduction in viral load, or levels of hepatitis B virus (HBV DNA) in the blood. HBeAg or e-antigen, is a viral protein associated with hepatitis B infections, and is found in the blood only when there is virus present.

The primary endpoint for the study was mean reduction in HBV DNA levels at week 12. The secondary endpoints included the mean change in viral load from baseline through week 96, the proportion of patients in each treatment group who achieved ALT normalization, HBeAg loss and HBe seroconversion, and safety.

Sixty-nine patients were randomized in the study and of these, 65 completed the first 12 weeks. Patients in this study received either 0.5 mg of BARACLUDE® (entecavir) once daily (n=33) or 10 mg of adefovir once daily (n=32) for a minimum of 52 weeks. Patients in the BARACLUDE treatment group had a mean baseline viral load of 10.26 log10 copies/mL. Patients in the adefovir treatment group had a mean baseline viral load of 9.88 log10 copies/mL.

According to study protocol, patients who achieved a treatment response at 52 weeks discontinued treatment and entered a follow-up monitoring phase. Three BARACLUDE-treated patients and four adefovir-treated patients met this criterion and entered the follow-up monitoring phase lasting up to 48 weeks. Patients who did not achieve a treatment response at 52 weeks continued on study to 96 weeks. Treatment response in this study is defined as HBeAg seroconversion and viral load less than 104 copies/mL for 24 weeks, with undetectable viral load at the end of the 24-week period.