EculizumabSoliris
Treatment of patients with neuromyelitis optica spectrum disorder (NMOSD) who are aquaporin-4 positive (AQP4+) with an Expanded Disability Status Scale (EDSS) score ≤ 7, and who have either frequent relapses or a prior immunosuppressive event.
Decisions on record
- Meeting Nov 2021 Not recommended Neuromyelitis optica spectrum disorder (NMOSD)
- Meeting Nov 2021 Not recommended Atypical haemolytic uraemic syndrome (aHUS)
- Meeting Nov 2020 Not recommended Neuromyelitis optica spectrum disorder (NMOSD)
- Meeting Mar 2018 Not recommended Atypical haemolytic uraemic syndrome (aHUS) in end stage renal disease (ESRD)
- Meeting Jul 2017 Recommended Atypical haemolytic uraemic syndrome (aHUS) in end stage renal disease (ESRD)
- Meeting Mar 2016 Not recommended atypical Haemolytic Uraemic Syndrome (aHUS) following kidney transplantation no PSD
- Meeting Nov 2015 Noted Atypical Haemolytic Uraemic Syndrome (aHUS) no PSD
- Meeting Mar 2014 Recommended Soliris® Alexion Pharmaceuticals Australasia Pty Ltd Atypical Haemolytic Uraemic Syndrome (aHUS) Re-submission to request Section 100 (Highly Specialised Drugs Program) or LSDP listing for atypical Haemolytic Uraemic Syndrome (aHUS). Patients with active, progressive thrombotic microangiopathy (TMA)
4 earlier decisions
- Jul 2012 Recommended Paroxysmal nocturnal haemoglobinuria no PSD
- Jul 2010 Deferred Monoclonal antibody for use in paroxysmal nocturnal haemoglobinuria
- Mar 2009 Not recommended Treatment of patients with paroxysmal nocturnal haemoglobinuria (PNH) to reduce haemolysis.
- Jul 2008 Not recommended Paroxysmal nocturnal haemoglobinuria
Access path
- TGA registered · Soliris
TGA label narrower than the PBS population
- Jul 2008Not recommended
unacceptably high and highly uncertain ICER (>$200,000 per death avoided), equivocal evidence of mortality benefit…
- ↻ resubmittedMar 2009Recommended
Evidence: RCT → RCT | Single-arm
- Jul 2010Recommended · restricted
Comparator changed: best supportive care → supportive care
- Jul 2010Recommended
Comparator changed: best supportive care → supportive care
- Mar 2013Recommended
Comparator changed: best supportive care → supportive care (plasma exchange/plasma…
- Mar 2014Recommended · restricted
Comparator changed: supportive care (plasma exchange/plasma infusion, dialysis, renal…
- Aug 2014Noted
Comparator changed: best supportive care (plasma exchange/infusion, dialysis, and/or…
- Jul 2017Recommended · restricted
Comparator changed: Supportive care / plasma therapy → long-term dialysis, renal…
- Mar 2018Not recommended
Comparator changed: long-term dialysis, renal transplantation with prophylactic plasma…
- Nov 2020Not recommended
Comparator changed: Discontinuation of eculizumab therapy with monitoring for recurrence…
- Nov 2021Not recommended
From the public summary
The PBAC did not recommend the listing of eculizumab for the treatment of patients with neuromyelitis optica spectrum disorder (NMOSD) who are aquaporin-4 positive (AQP4+). Although the PBAC considered that eculizumab was more effective than best supportive care in reducing relapses, the magnitude of this effect on disability progression and quality of life remained highly uncertain.PSD · Nov 2021
The PBAC welcomed the input from the health professional and organisations via the Consumer Comments facility which outlined the disease progression of NMOSD and the effects of NMOSD on quality of life, as well as the use of current treatments, including rituximab.PSD · Nov 2021
who have had a prior immunosuppressive event, therefore Not addressed in the resubmission the cost effectiveness of eculizumab in this population could not be assessed. (para 7.13, eculizumab PSD, November 2020) 2PSD · Nov 2021
The PBAC noted that the majority of the incremental benefits, which included patients treated with eculizumab Not addressed in the resubmission averaging 1.6 fewer relapses and gaining 4.6 life years compared to those treated with placebo, occurred in the extrapolated period (para 7.15, eculizumab PSD, November 2020) The submission assumed 7% of relapses were fatal based on Mealy 2018, an observational study.PSD · Nov 2021
The resubmission described eculizumab as superior in terms of efficacy and non- inferior in terms of safety compared to placebo. The PBAC again considered that eculizumab was more effective than best supportive care in reducing relapses; however, the magnitude of this effect on disability progression and quality of life outcomes was highly uncertain. The PBAC considered that the claim of non-inferior comparative safety was reasonable.PSD · Nov 2021
As no new clinical data were presented for the comparison between eculizumab and best supportive care, the PBAC noted that a number of issues from November 2020 remained unresolved in the resubmission including:PSD · Nov 2021
The PBAC noted and welcomed the input from health care professionals (8) and organisations (2) via the Consumer Comments facility on the PBS website. The comments from health care professionals described the clinical need for new, effective treatments for NMOSD such as eculizumab and noted that eculizumab was associated with fewer side effects than other available treatments.PSD · Nov 2021
The PBAC noted the advice received from MS Australia which highlighted the differences between multiple sclerosis (MS) and NMOSD, including the fact that NMOSD relapses are generally more severe, last longer and occur more often than MS relapses and that most patients do not recover completely from relapses.PSD · Nov 2021
Cost-effectiveness
ICER values are commercially sensitive and redacted in the public document. The document references redacted pricing and economic model values throughout.
Given the high requested price of eculizumab and the uncertain magnitude of benefit in terms of disability progression, the PBAC considered that the proposed restriction should align with the inclusion criteria of the PREVENT trial in terms of number of prior relapses and EDSS score. PBAC · 2020
Decision context
PopulationAdult patients with NMOSD who are AQP4-IgG positive with an EDSS score of 0–7 and who have had at least one relapse in the last 12 months with at least two relapses in the last 24 months, or at least two relapses in the last 12 months or three relapses in the last 24 months despite immunosuppressive therapy, or who have experienced immunosuppression-associated serious adverse events requiring treatment discontinuation.
Risk sharingThe resubmission included a proposal for a Risk Sharing Agreement (RSA) with an updated patient number cap, based on the total number of patients on treatment, reducing the cap compared to the first submission. A special pricing arrangement (SPA) with an effective price based on a redacted % reduction from the published price was also proposed.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2021 | Not recommended | best supportive care | — | RCT · Reduction in relapse frequency |
| Nov 2020 | Not recommended | best supportive care | — | RCT · Time to first relapse |
| Mar 2018 | Not recommended | Discontinuation of eculizumab therapy with monitoring for recurrence of thrombotic microangiopathy | — | Single-arm · Other |
| Jul 2017 | Recommended · restricted | long-term dialysis, renal transplantation with prophylactic plasma exchange/infusion, and treatment initiation at recurr | — | Single-arm · Other |
| Aug 2014 | Noted | Supportive care / plasma therapy | — | Single-arm · TMA response, haematologic normalisation, renal function improvement |
| Mar 2014 | Recommended · restricted | best supportive care (plasma exchange/infusion, dialysis, and/or renal transplant) | — | Single-arm · TMA response |
| Mar 2013 | Recommended | supportive care (plasma exchange/plasma infusion, dialysis, renal transplant) | $1m–4m | Single-arm · TMA intervention rate, renal function, platelet count, quality of life |
| Jul 2010 | Recommended · restricted | supportive care | — | RCT, Registry, Cost-minimisation |
| Jul 2010 | Recommended | best supportive care | — | Registry |
| Mar 2009 | Recommended | best supportive care | $200k | RCT | Single-arm |
| Jul 2008 | Not recommended | best supportive care | $200k | RCT · OS, PFS, QoL |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| PREVENT (ECU-NMO-301) | Ph 3 | 119 | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | completed |
Consumer voice
Health care professionals (8) and organisations (2) provided input highlighting the clinical need for new effective NMOSD treatments like eculizumab, noting it has fewer side effects than alternatives. MS Australia emphasized that NMOSD relapses are more severe and frequent than MS relapses, with approximately 25% of patients continuing to relapse on rituximab.
eculizumab was associated with fewer side effects than other available treatments Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to AQP4+ patients with specific relapse frequency criteria and EDSS ≤7; TGA label has no such clinical restrictions.