AgomelatineAGOMELATINE-WGR
Not recommended Mental healthFirst-line line
Treatment of major depressive disorders in adults, including prevention of relapse.
4
Submissions
3 resub
2010–12
On the record
$15k–30k
ICER range
1 sourced ICER · 2010
Cost-min
Cost basis
Decisions on record
- Meeting Mar 2012 Not recommended Treatment of major depression in adults including prevention of relapse.
- Meeting Jul 2011 Not recommended Treatment of major depression in adults including prevention of relapse.
- Meeting Nov 2010 Not recommended Anti-depressant
Access path
- TGA registered · AGOMELATINE-WGR
TGA label narrower than the PBS population
- Nov 2010Recommended
vs venlafaxine
- Jul 2011Not recommended
Superior clinical effectiveness and safety over SSRIs not demonstrated, concerns about selective exclusion of earlier…
- ↻ resubmittedMar 2012Recommended
Comparator changed: SSRIs (sertraline, citalopram, escitalopram, fluoxetine and…
- Mar 2012Recommended
Comparator changed: SSRIs (sertraline, citalopram, escitalopram, fluoxetine and…
- PBS listing
RecommendedDeferredNot recommended
From the public summary
Economic analysis
The PBAC considered the utilisation estimates in the resubmission to be highly uncertain due to the potential for usage outside the requested restriction including use in the management of sleep disorders, uncertainty in the relative substitutions of SSRIs and SNRIs, uncertainty in the estimated market uptake rates and the assumed differences in the duration of therapy.PSD · Mar 2012
The PBAC therefore rejected the submission on the basis that superior clinical effectiveness and safety over SSRIs had not been demonstrated. The PBAC further considered that non- inferior efficacy and superior safety to venlafaxine had not been demonstrated.PSD · Mar 2012
Comparative effectiveness
The resubmission presented no new trial data comparing agomelatine with venlafaxine (CL3-035 and CL3-036). The main outcome of HAM-D17 & Montgomery-Asberg depression rating scale (MADRS) scores were the secondary outcomes of the agomelatine vs venlafaxine trials. The primary outcomes were the Leeds Sleep Evaluation Questionnaire (CL3-035) and the Sex Effects Scale score (CL3-036).PSD · Jul 2011
The results of CL3-035 and CL3-036 have been previously reported in the November 2010 PSD. Agomelatine versus SSRIs:PSD · Jul 2011
Cost-effectiveness
Cost-minimisation analysis presented; PBAC rejected the analysis as it was not supported by the clinical evidence for non-inferior efficacy and safety to venlafaxine.
The PBAC considered the equi-effective doses estimated in the resubmission of agomelatine 28.5 mg and venlafaxine 83.8 mg to be uncertain, noting that the dose of venlafaxine in trial CL3-035 (150 mg), on which the equi-effective doses were based, was less than the maximum recommended dose in the TGA-approved product information (225 mg). PBAC · 2012
ICER uncertainEconomic model disputed ×2Surrogate endpoint
Decision context
PopulationAdults with major depressive disorders as first-line treatment.
Why it was knocked back
- superior clinical effectiveness and safety over SSRIs not demonstrated, non-inferior efficacy and superior safety to venlafaxine not demonstrated, uncertain equi-effective doses, cost-minimisation analysis not supported by clinical evidence, exclusion of trials on assay sensitivity grounds not appropriate, exclusion of liver function test costs from economic model inappropriate, highly uncertain utilisation estimates
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2012 | Recommended | SSRIs (fluoxetine, sertraline, escitalopram); venlafaxine | — | RCT, Single-arm · OS | PFS | DFS | ORR | QoL | Surrogate |
| Mar 2012 | Recommended | venlafaxine and selective serotonin re-uptake inhibitors (SSRIs) | — | RCT |
| Jul 2011 | Not recommended | SSRIs (sertraline, citalopram, escitalopram, fluoxetine and fluvoxamine) | — | RCT, Meta-analysis · HAM-D17, CGI-I, CGI-S |
| Nov 2010 | Recommended | venlafaxine | $15k–30k | RCT · null |
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to first-line use; TGA label includes all adults and relapse prevention without treatment-sequencing limitation.