AlemtuzumabLemtrada
Relapsing remitting multiple sclerosis (RRMS); specifically the resubmission sought reimbursement of up to two additional courses of treatment for patients experiencing relapses or MRI lesion activity after initial two courses.
Decisions on record
- Meeting Nov 2018 Not recommended Relapsing remitting multiple sclerosis (RRMS)
- Meeting Nov 2014 Not recommended 10 mg/mL injection, 1 x 2 mL vial, Lemtrada® Genzyme (A Sanofi company) Pty Ltd Change to recommended listing (Minor submission) Treatment of relapsing forms of multiple sclerosis (MS) for patients with active disease defined by clinical or imaging features to slow the accumulation of physical disab
- Meeting Jul 2014 Recommended 10 mg/mL injection, 1 x 2 mL vial Lemtrada® Genzyme (A Sanofi company) Pty Ltd New listing (Major submission) Multiple sclerosis Section 100 (Highly Specialised Drugs Program) Authority required listing for the treatment of clinically definite relapsing-remitting multiple sclerosis in ambulatory pat
Access path
- TGA registered · Lemtrada
TGA label narrower than the PBS population
- Jul 2014Recommended · restricted
vs fingolimod and natalizumab
- Nov 2014Not recommended
Comparator changed: fingolimod and natalizumab → fingolimod and natalizumab (50:50…
- Nov 2018Not recommended
Comparator nominated by sponsor was the intervention itself and therefore inappropriate; cost-minimisation analysis…
From the public summary
7.1 The PBAC did not recommend the request to increase the price per vial for alemtuzumab for relapsing remitting multiple sclerosis (RRMS) based on a claim of extended clinical benefit from two years to six years. The PBAC also did not recommend a change to the current listing to include an additional continuation restriction for the third and fourth courses of alemtuzumab for patients with RRMS who meet proposed re-treatment criteria.PSD · Nov 2018
7.2 The PBAC noted and welcomed the consumer comments received from MS Research Australia which highlighted that patients value additional treatment options for multiple sclerosis.PSD · Nov 2018
6.36 The resubmission presented a cost analysis which compared the cost per year of benefit with two courses of alemtuzumab (cost of two courses divided by two years of benefit) with that for up to four courses of alemtuzumab (cost of up to 4 courses divided by up to 6 years of benefit).PSD · Nov 2018
6.37 The most critical issue affecting the validity of the cost analysis presented in the resubmission is that the resubmission’s nominated comparator is likely to be inappropriate, and a cost effectiveness analysis against an alternative comparator (fingolimod, natalizumab, ocrelizumab or cladribine) should have been the basis for the analysis.PSD · Nov 2018
patients remaining relapse-free may provide an informative basis rather than patients remaining relapse- for assessing durability of effect and as well as proportions of free over the time period. It did not patents being re-treated if the necessary links between individual appear that the necessary links between patients could be adequately demonstrated (paragraph 7.6). individual patients were demonstrated. 3PSD · Nov 2018
Source: Alemtuzumab November 2014 PSD For more detail on PBAC’s view, see section 7 PBAC outcome.PSD · Nov 2018
6.2 The PBAC noted and welcomed the input from the organisation MS Research Australia via the Consumer Comments facility on the PBS website. The comments described a range of benefits of treatment with alemtuzumab including stabilising or improving disabilities (as demonstrated by EDSS scores) and its impact on conversion from RRMS to secondary progressive MS reported in the CARE-MS I and II trials.PSD · Nov 2018
Cost-effectiveness
No ICER stated. The resubmission presented a cost-minimisation analysis but PBAC found it inadequate; no incremental cost-effectiveness ratio was calculated or provided in the public document.
The PBAC agreed with the ESC that it was unreasonable to conflate the requested price increase which is based on the assumption of the same level of benefit being maintained in all patients, with the request for up to two additional courses of treatment as the requirement for additional courses of treatment indicates that the extent of sustained treatment benefit is not equivalent for all patients. PBAC · 2018
Decision context
PopulationAdult patients with relapsing remitting multiple sclerosis; two subpopulations: (1) those who do not experience relapses or new/enlarging brain or spinal cord lesions after two PBS-subsidised courses, and (2) those who experience one or more relapses or two or more new/enlarging lesions after two PBS-subsidised courses.
Why it was knocked back
- Comparator nominated by sponsor was the intervention itself and therefore inappropriate; cost-minimisation analysis based on assumption of equivalent sustained benefit in all patients was unreasonable given that additional courses indicate differential treatment benefit; absence of cost-utility analysis to account for differences in risk/benefit profile; PBAC required data comparing up to two additional courses against alternative RRMS medicines or no further treatment rather than against the initially funded two courses
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2018 | Not recommended | Fingolimod, natalizumab, ocrelizumab, cladribine, or other PBS-listed RRMS disease modifying therapies; for patients rem | — | RCT · Annualised relapse rate, disability accumulation, proportion remaining relapse-free, MRI measures |
| Nov 2014 | Not recommended | fingolimod and natalizumab (50:50 weighting) | — | RCT · Relapse rate |
| Jul 2014 | Recommended · restricted | fingolimod and natalizumab | — | RCT · Relapse rate and disability progression |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| CAMMS03409 | Ph 4 | 1,062 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emerg… | completed |
Consumer voice
MS Research Australia provided input supporting alemtuzumab treatment, highlighting benefits including stabilisation or improvement of disabilities, reduced conversion to secondary progressive MS, and improved quality of life for patients and families.
The comments described a range of benefits of treatment with alemtuzumab including stabilising or improving disabilities (as demonstrated by EDSS scores) and its impact on conversion from RRMS to secondary progressive MS reported in the CARE-MS I and II trials. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to patients with documented disease activity (relapses or MRI lesions) after initial courses; TGA label permits treatment without this activity requirement.