Deutetrabenazine
Treatment of chorea associated with Huntington's disease in patients who have failed prior tetrabenazine treatment due to intolerance or inadequate response.
Decision on record
- Meeting Mar 2021 Not recommended Chorea associated with Huntington's disease
From the public summary
The PBAC did not recommend the listing of deutetrabenazine for the treatment of chorea associated with Huntington’s Disease (HD) in patients who have failed prior tetrabenazine treatment due to intolerance or inadequate response.PSD · Mar 2021
The PBAC acknowledged the devastating impact HD has on patients and their families and considered there was a high clinical need for new therapies to assist patients with 28PSD · Mar 2021
Figure 1: Responder analyses of change in UHDRS Total Maximal Chorea score from baseline to maintenance period (average of Week 9 and Week 12 values) in the FIRST-HD trial Source: Figure 2-2 of the submission Abbreviations: SD-809, deutetrabenazine; TMC, Total Maximal Chorea The proportion of patients with treatment success based on patient or physician global impression is summarised in the table below. 10PSD · Mar 2021
The change in other relevant symptoms scores and quality of life measures with deutetrabenazine and placebo treatment in the FIRST-HD trial is summarised in the table below.PSD · Mar 2021
to placebo Source: Table 1-1 of the submission The ESC advised the placement of deutetrabenazine in the submission as second or third line therapy was inappropriate and not supported by the available evidence. The ESC noted there was no evidence presented in the submission for the requested second or third line setting after failure (or inability to tolerate maximal dosing) of tetrabenazine.PSD · Mar 2021
On this basis, the ESC considered the most appropriate placement of deutetrabenazine is in first-line therapy as an alternative to tetrabenazine and that clinical and economic comparisons should be undertaken on that basis. Therefore, the ESC considered the clinical and economic comparisons presented in this submission were not informative for decision-making.PSD · Mar 2021
The PBAC noted and welcomed the input from consumers (2) and the Coalition of Australian Huntington’s Associations in support of the listing. The PBAC noted the individuals and organisations highlighted impact of HD on patients and families and 6PSD · Mar 2021
In its Pre-PBAC Response, the sponsor indicated it was amenable to a Risk Sharing Arrangement. For more detail on PBAC’s view, see section 7 PBAC outcome.PSD · Mar 2021
Cost-effectiveness
No ICER values are stated in the public text. The submission was based on a cost-effectiveness analysis versus placebo, but the PSD does not disclose numeric ICER figures.
Decision context
PopulationPatients with chorea associated with Huntington's disease who have failed prior tetrabenazine treatment due to intolerance or inadequate response.
Why it was knocked back
- Proposed placement as second or third-line therapy unsupported by evidence; no clinical data for efficacy and safety in subsequent-line treatment setting after tetrabenazine failure; proposed restriction inappropriate and clinically inconsistent; risk of high leakage to first-line use; most appropriate clinical placement is first-line therapy, for which economic model was not provided and sponsor stated first-line listing would not be viable at comparable price to tetrabenazine
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2021 | Not recommended | placebo | — | RCT |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| FIRST-HD | Ph 3 | 90 | Change From Baseline (Average of Screening and Day 0) in the Average TMC Scores From Weeks… | completed |
Consumer voice
Two consumers and the Coalition of Australian Huntington's Associations supported the listing, highlighting the impact of HD on patients and families. A patient treated with deutetrabenazine reported better symptom control and improved quality of life due to longer periods of consistent physical functioning and reduced social anxiety compared to tetrabenazine.
deutetrabenazine has provided better symptom control and improved quality of life as the drug does not wear off in the same way as tetrabenazine, allowing for longer periods of consistent physical functioning and reduced social anxiety Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to patients who failed prior tetrabenazine treatment; TGA label includes all Huntington's chorea patients without this prerequisite.