Adefovir Dipivoxil 10 mg for the Treatment of Chronic Hepatitis B

8/14/02


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Table of Contents

Adefovir Dipivoxil 10 mg for the Treatment of Chronic Hepatitis B

Proposed Indication

Consultants

Agenda

Chronic Hepatitis B A Global Healthcare Issue

Current Therapies for Chronic Hepatitis B

Goals for New Antiviral Therapies for Chronic Hepatitis B

Adefovir Dipivoxil

In Vitro Activity of Adefovir Wild-type and Lamivudine-resistant HBV

Preclinical Pharmacology and Toxicology

Adefovir Dipivoxil 10 mg Clinical Pharmacokinetics

Adefovir Dipivoxil in Chronic Hepatitis B Dose Selection

Chronic Hepatitis B Exposure to Adefovir Dipivoxil

Clinical Efficacy and Safety

Adefovir Dipivoxil Pivotal Studies

Studies 437 and 438 Key Inclusion Criteria

Studies 437 and 438 Baseline Characteristics (ITT)

PPT Slide

Studies 437 and 438 Primary Endpoint

Studies 437 and 438 (ITT) 48 Weeks Primary Endpoint: Improvement in Liver Histology

Studies 437 and 438 Integrated 48 Weeks (ITT) Histological Improvement by Demographic Characteristics

Studies 437 and 438 Integrated 48 Weeks (ITT) Histological Improvement by Baseline HBV Characteristics

Studies 437 and 438 Secondary Endpoints

Studies 437 and 438 (ITT) 48 Weeks Necroinflammation Ranked Assessment

PPT Slide

Studies 437 and 438 Median Change from Baseline in HBV DNA

Studies 437 and 438 (ITT) 48 Weeks Serum HBV DNA < 400 copies/mL

Studies 437 and 438 (ITT) 48 Weeks ALT Normalization

Study 437 (ITT) 48 Weeks HBeAg Loss and Seroconversion

Study 437 and 438 Efficacy Beyond 48 Weeks

Study 437 and 438 All ADV 10 mg (n=492) Efficacy Beyond 48 weeks

Studies 437 and 438 ADV 10 mg Efficacy Summary

Studies 437 and 438 Safety of Adefovir Dipivoxil 10 mg

PPT Slide

Studies 437 and 438 Integrated 0-48 Weeks Grade 1-4 Treatment-Related Adverse Eventsa

Studies 437 and 438 Integrated 0-48 Weeks Grade 3-4 Laboratory Abnormalitiesa

Studies 437 and 438 Integrated 0-48 Weeks Grade 1-4 Renal Laboratory Parameters

Studies 437 and 438 Integrated 0-48 Weeks Renal Laboratory Abnormalities

Studies 437 and 438 0-48 Weeks Renal Laboratory Abnormalities

Studies 437 and 438 Integrated ADV 10 mg Renal Laboratory Abnormalities 0-96 Weeks

Study 437 and 438 All ADV 10 mg Resolution of ? 0.3 mg/dL Increases in Serum Creatinine 0-96 Weeks (n=29)

Studies 437 and 438 Integrated 0-48 Weeks ALT Elevations > 10 x ULN

Studies 437 and 438 Integrated ADV 10 mg ALT Elevations > 10 x ULN 48-96 Weeks

Studies 437 and 438 Integrated 0-96 Weeks Adefovir Dipivoxil 10 mg Safety Summary

Adefovir Dipivoxil 30 mg Efficacy and Safety

Study 437 (ITT) Efficacy Results 48 Weeks

Study 437 Renal Laboratory Abnormalities 48 Weeks

Study 437 Assessment of Adefovir Dipivoxil 30 mg

Resistance Surveillance

Studies 437 and 438 Resistance Surveillance

Studies 437 and 438 Resistance Surveillance Results

Supportive Studies

Lamivudine Resistance

Study 435 Compassionate Access

Study 435 Mortality Rates in Advanced Liver Disease

Study 435 Baseline Characteristics

Study 435 Baseline HBV Disease Characteristics

Study 435 Median Change from Baseline in HBV DNA

Study 435 Week 48 Secondary Efficacy Endpoints

Study 435 Survival

Study 435 Patient Disposition

Study 435 Renal Laboratory Abnormalities by Week 96

Study 435 Post-Transplantation Patients with Confirmed Increases in Serum Creatinine ? 0.5 mg/dL from Baseline (n=26)

Study 435 Pre-Transplantation Patients with Confirmed Increases in Serum Creatinine ? 0.5 mg/dL from Baseline (n=15)

Adefovir Dipivoxil 10 mg Dosing Recommendations in Patients with or at risk of Renal Impairment

Study 435 Summary

Lamivudine-Resistant HBV Other Supportive Studies

PPT Slide

Study 461 ALT Normalization Week 48

Further Studies

Further Studies

Adefovir Dipivoxil for the Treatment of Chronic Hepatitis B

Proposed Indication

Author: Justin Drew