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Adefovir DipivoxilAPO-ADEFOVIR

Recommended HepatologyRestrictedSecond-line line

Chronic hepatitis B in patients who have failed antihepadnaviral therapy, now with the addition of concurrent use with lamivudine in lamivudine-resistant patients.

7
Submissions
5 resub
2006–07
On the record
$15k–75k
ICER range
4 sourced ICERs · 2006–2007
Cost-min
Cost basis

Decisions on record

4 decisions
  • Meeting Nov 2007 Recommended Hepatitis B
  • Meeting Nov 2007 Recommended Hepatitis B
  • Meeting Nov 2006 Recommended Chronic hepatitis B. no PSD
  • Meeting Jul 2004 Recommended Used for the treatment of Hepatitis B no PSD

Access path

7 submissions · public record
  1. TGA registered · APO-ADEFOVIR

    TGA label narrower than the PBS population

  2. Jul 2006
    Not recommended

    Trial population not representative of requested PBS population (advanced liver disease and post-transplant patients)…

  3. Jul 2006
    Not recommended

    Trial population not representative of PBS listing population (HBeAg-positive, compensated, nucleos(t)ide-naïve only…

  4. Jul 2006
    Not recommended

    patients in key trial not representative of population for whom PBS listing sought, comparator in clinical trial not…

  5. ↻ resubmitted
    Mar 2007
    Recommended

    Comparator changed: lamivudine monotherapy and sequential adefovir → lamivudine…

  6. Mar 2007
    Recommended

    Comparator changed: lamivudine monotherapy and sequential adefovir → lamivudine…

  7. Nov 2007
    Recommended · restricted

    Comparator changed: lamivudine monotherapy followed by adefovir dipivoxil monotherapy…

  8. Nov 2007
    Recommended · restricted

    Comparator changed: lamivudine monotherapy followed by adefovir dipivoxil monotherapy…

  9. PBS listing · Restricted
RecommendedDeferredNot recommended

From the public summary

Verbatim · PSD text · may span indications
Clinical claim
3. Registration Status Adefovir dipivoxil tablet 10 mg was registered on 16 September 2003 by the TGA for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases or histologically active disease. 4.PSD · Mar 2007
(greater than 1.2 times the upper limit of normal) serum ALT levels. Patients must have received concurrent antihepadnaviral therapy of greater than or equal to 6 months. Patients may receive PBS subsidised treatment of lamivudine in combination with adefovir for the initial 3 months only of PBS subsidised adefovir, unless patients have advanced liver disease (evidence of cirrhosis on liver biopsy or a Child Pugh Turcotte score greater than 5), in which …PSD · Mar 2007

Cost-effectiveness

4 sourced ICERs · 2006–2007

Cost-minimisation analysis based on cost offsets; no formal ICER calculated.

The PBAC noted that the cost offsets presented in the submission remained uncertain despite two cost offsets models being presented. PBAC · 2007
ICER uncertain ×3Economic model disputed ×4Surrogate endpoint ×2

Decision context

PopulationAdult patients with chronic hepatitis B who have failed antihepadnaviral therapy (specifically lamivudine-resistant patients), with repeatedly elevated HBV DNA levels or elevated serum ALT levels, excluding pregnant/breastfeeding women of child-bearing age.

Submission history

7 entries
DecidedOutcomeComparatorICEREvidence
Nov 2007 Recommended · restricted adefovir monotherapy RCT · Other
Nov 2007 Recommended · restricted adefovir monotherapy Meta-analysis
Mar 2007 Recommended lamivudine monotherapy followed by adefovir dipivoxil monotherapy (for lamivudine-sensitive HBV) and adefovir dipivoxil $45k–75k RCT
Mar 2007 Recommended lamivudine monotherapy followed by adefovir dipivoxil monotherapy (for lamivudine-sensitive HBV); adefovir dipivoxil mon $15k–75k Registry
Jul 2006 Not recommended Lamivudine monotherapy and lamivudine and sequential adefovir $45k–75k RCT, Registry · surrogate (HBV DNA)
Jul 2006 Not recommended Lamivudine monotherapy and lamivudine and sequential adefovir $45k–75k RCT, Registry · surrogate (HBV DNA)
Jul 2006 Not recommended lamivudine monotherapy and sequential adefovir RCT · HBV DNA change

Similar precedents

By decision profile

Regulatory · TGA

Label narrower than PBS population — PBAC restricts to treatment-experienced patients (failed prior antihepadnaviral therapy), whereas TGA label includes all treatment-naive adults with active replication.