2-Year Adefovir Treatment Appears Safe, Effective in HBeAg-Positive Chinese Pati

[Guest guest]

CCO Official Conference Coverage of the Shanghai-Hong Kong International

Liver Congress 2006

2-Year Adefovir Treatment Appears Safe, Effective in HBeAg-Positive Chinese

Patients Chronically Infected With HBV

Randomized, prospective, placebo-controlled trial with open-label and

double-blind components

Summary of Key Conclusions

2-year treatment with adefovir provided sustained virologic, biochemical,

and serologic responses in Chinese patients with HBeAg-positive chronic

hepatitis B infection, regardless of baseline YMDD mutations

Resuming adefovir after 12-week treatment interruption restored all

responses

Adefovir safe, well tolerated, and rarely led to development of resistance

mutations

Background

Adefovir, a nucleotide analogue reverse transcriptase inhibitor active

against HBV

Effective in patients with lamivudine-resistant HBV

Current study evaluated safety and efficacy of 2 years¡¯ adefovir therapy in

Chinese patients with HBeAg-positive chronic hepatitis B

Also investigated impact of 12-week treatment delay or interruption

Schematic of Study Design

Eligibility

Inclusion criteria

18-65 years of age

HBsAg positive > 6 months

HBeAg positive > 6 months

HBV DNA ¡Ý 106 copies/mL

ALT ¡Ý 2 x upper limit of normal (ULN) within prior 6 months

ALT 1-10 x ULN at screening

Exclusion criteria

Hepatocellular carcinoma

Decompensated liver disease

Kidney dysfunction

Coinfection with HIV or other hepatitis viruses

Amylase > 2 x ULN

Lipase > 2 x ULN

Lamivudine treatment in past 3 months

Baseline Characteristics

N = 480

YMDD mutation: 94 (19.6%)

Description of Current Analysis

Virologic and biochemical endpoints assessed

Change in HBV DNA

Proportion of patients achieving HBV DNA ¡Ü 300 copies/mL

ALT normalization

HBeAg loss

Durable HBeAg seroconversion: response for ¡Ý 6 months (at 3 consecutive

measurements taken at least 3 months apart)

HBeAg loss,

HBeAb gain,

HBV DNA ¡Ü 300 copies/mL, and

Normal ALT

Patients with ¡Ý 1 log10 increase in HBV DNA from nadir value underwent

sequence analysis for adefovir resistance mutations at Weeks 52 and 104

Modified intent-to-treat analysis

Main Findings

2-year treatment with adefovir provided continued benefits

Persistent serum HBV DNA suppression

Continuous ALT normalization

Increased rate of HBeAg loss and HBeAg seroconversion

Parameter

Placebo-Adefovir Arm

Continuous Adefovir Arm

Adefovir-Placebo-Adefovir Arm

Week 52

(n = 120)

Week 104

(n = 119)

Week 52

(n = 240)

Week 104

(n = 236)

Week 52

(n = 120)

Week 104

(n = 119)

Median change in HBV DNA, log10 copies/mL

-5.0

-5.3

-4.5

-5.0

-0.2

-4.7

HBV DNA ¡Ü 300 copies/mL, %

30

45

28

42

1

41

ALT normalization, %

69

74

79

78

21

71

HBeAg loss, %

20

29

13

18

9

28

HBeAg seroconversion, %

18

22

8

14

7

20

Resumption of adefovir restored virologic and biochemical responses after

12-week treatment interruption with placebo

At Year 2, 9.5% of 474 patients demonstrated durable HBeAg seroconversion

Adefovir therapy stopped in these patients

Presence of YMDD at baseline had no effect on adefovir efficacy at Year 2

No adefovir resistance mutations observed at Year 1; resistance mutations

rare at Year 2 (1.3%)

3 patients had N236T

3 patients had A181V

Other Outcomes

2 patients (0.6%) had adverse events requiring discontinuation

Hepatitis B flare (n = 1)

Gastric carcinoma (n = 1)

Drug-related adverse events observed in 1.7% of patients (n = 8) through

Year 2

All mild or moderate, including

Rash

Nasopharyngitis

Creatine phosphokinase increase

ALT elevation

Alopecia

Serious adverse events observed in 1.7% of patients (n = 8) through Year 2

None drug related

Hepatitis B flare

Gastric carcinoma (fatal in 1 patient)

Intestinal obstruction

Diabetes

Liver carcinoma

3 patients had serum creatinine increases > 0.5 mg/dL from baseline to Year

2

None showed peak value above normal range

No patients experienced serum phosphorus decrease ¡Ü 1.4 mg/dL

Safety not affected by baseline YMDD mutations

Reference

Zeng MD, Mao YM, Yao GB, et al. Efficacy of two years therapy with adefovir

dipivoxil (ADV) in Chinese patients with HBeAg positive chronic hepatitis B

(CHB). Program and abstracts of the 2006 Shanghai-Hong Kong International

Liver Congress; March 25-28, 2006, 2005; Shanghai, China. Abstract 3.

http://clinicaloptions.com/Hepatitis/Conference%20Coverage/Shanghai%202006/Capsu\

les/3.aspx?Track=Hepatitis+B

_________________________________________________________________

Don’t just search. Find. Check out the new MSN Search!

http://search.msn.click-url.com/go/onm00200636ave/direct/01/

[Guest guest]

CCO Official Conference Coverage of the Shanghai-Hong Kong International

Liver Congress 2006

2-Year Adefovir Treatment Appears Safe, Effective in HBeAg-Positive Chinese

Patients Chronically Infected With HBV

Randomized, prospective, placebo-controlled trial with open-label and

double-blind components

Summary of Key Conclusions

2-year treatment with adefovir provided sustained virologic, biochemical,

and serologic responses in Chinese patients with HBeAg-positive chronic

hepatitis B infection, regardless of baseline YMDD mutations

Resuming adefovir after 12-week treatment interruption restored all

responses

Adefovir safe, well tolerated, and rarely led to development of resistance

mutations

Background

Adefovir, a nucleotide analogue reverse transcriptase inhibitor active

against HBV

Effective in patients with lamivudine-resistant HBV

Current study evaluated safety and efficacy of 2 years¡¯ adefovir therapy in

Chinese patients with HBeAg-positive chronic hepatitis B

Also investigated impact of 12-week treatment delay or interruption

Schematic of Study Design

Eligibility

Inclusion criteria

18-65 years of age

HBsAg positive > 6 months

HBeAg positive > 6 months

HBV DNA ¡Ý 106 copies/mL

ALT ¡Ý 2 x upper limit of normal (ULN) within prior 6 months

ALT 1-10 x ULN at screening

Exclusion criteria

Hepatocellular carcinoma

Decompensated liver disease

Kidney dysfunction

Coinfection with HIV or other hepatitis viruses

Amylase > 2 x ULN

Lipase > 2 x ULN

Lamivudine treatment in past 3 months

Baseline Characteristics

N = 480

YMDD mutation: 94 (19.6%)

Description of Current Analysis

Virologic and biochemical endpoints assessed

Change in HBV DNA

Proportion of patients achieving HBV DNA ¡Ü 300 copies/mL

ALT normalization

HBeAg loss

Durable HBeAg seroconversion: response for ¡Ý 6 months (at 3 consecutive

measurements taken at least 3 months apart)

HBeAg loss,

HBeAb gain,

HBV DNA ¡Ü 300 copies/mL, and

Normal ALT

Patients with ¡Ý 1 log10 increase in HBV DNA from nadir value underwent

sequence analysis for adefovir resistance mutations at Weeks 52 and 104

Modified intent-to-treat analysis

Main Findings

2-year treatment with adefovir provided continued benefits

Persistent serum HBV DNA suppression

Continuous ALT normalization

Increased rate of HBeAg loss and HBeAg seroconversion

Parameter

Placebo-Adefovir Arm

Continuous Adefovir Arm

Adefovir-Placebo-Adefovir Arm

Week 52

(n = 120)

Week 104

(n = 119)

Week 52

(n = 240)

Week 104

(n = 236)

Week 52

(n = 120)

Week 104

(n = 119)

Median change in HBV DNA, log10 copies/mL

-5.0

-5.3

-4.5

-5.0

-0.2

-4.7

HBV DNA ¡Ü 300 copies/mL, %

30

45

28

42

1

41

ALT normalization, %

69

74

79

78

21

71

HBeAg loss, %

20

29

13

18

9

28

HBeAg seroconversion, %

18

22

8

14

7

20

Resumption of adefovir restored virologic and biochemical responses after

12-week treatment interruption with placebo

At Year 2, 9.5% of 474 patients demonstrated durable HBeAg seroconversion

Adefovir therapy stopped in these patients

Presence of YMDD at baseline had no effect on adefovir efficacy at Year 2

No adefovir resistance mutations observed at Year 1; resistance mutations

rare at Year 2 (1.3%)

3 patients had N236T

3 patients had A181V

Other Outcomes

2 patients (0.6%) had adverse events requiring discontinuation

Hepatitis B flare (n = 1)

Gastric carcinoma (n = 1)

Drug-related adverse events observed in 1.7% of patients (n = 8) through

Year 2

All mild or moderate, including

Rash

Nasopharyngitis

Creatine phosphokinase increase

ALT elevation

Alopecia

Serious adverse events observed in 1.7% of patients (n = 8) through Year 2

None drug related

Hepatitis B flare

Gastric carcinoma (fatal in 1 patient)

Intestinal obstruction

Diabetes

Liver carcinoma

3 patients had serum creatinine increases > 0.5 mg/dL from baseline to Year

2

None showed peak value above normal range

No patients experienced serum phosphorus decrease ¡Ü 1.4 mg/dL

Safety not affected by baseline YMDD mutations

Reference

Zeng MD, Mao YM, Yao GB, et al. Efficacy of two years therapy with adefovir

dipivoxil (ADV) in Chinese patients with HBeAg positive chronic hepatitis B

(CHB). Program and abstracts of the 2006 Shanghai-Hong Kong International

Liver Congress; March 25-28, 2006, 2005; Shanghai, China. Abstract 3.

http://clinicaloptions.com/Hepatitis/Conference%20Coverage/Shanghai%202006/Capsu\

les/3.aspx?Track=Hepatitis+B

_________________________________________________________________

Don’t just search. Find. Check out the new MSN Search!

http://search.msn.click-url.com/go/onm00200636ave/direct/01/