Zilucoplan
Treatment of generalised myasthenia gravis (gMG) in adult patients with anti-acetylcholine receptor (AChR) antibody positive status who are refractory to conventional immunotherapies.
Decisions on record
- Meeting Mar 2025 Recommended Generalised myasthenia gravis (gMG), anti-acetylcholine receptor antibody positive
- Meeting Jul 2024 Not recommended Generalised myasthenia gravis anti-acetylcholine receptor antibody positive
Access path
- Jul 2024Not recommended
vs placebo
- ↻ resubmittedMar 2025Recommended · restricted
- PBS listing · Authority Required
From the public summary
8.1 The PBAC recommended the listing of zilucoplan for the treatment of generalised myasthenia gravis (gMG), on the basis that it should be available only under special arrangements under the Section 100 Highly Specialised Drugs Program. The PBAC recognised the high clinical need for new therapies to treat this condition, which has substantial impacts on patient quality of life.PSD · Mar 2025
OFFICIAL Public Summary Document – March 2025 PBAC Meeting of the available evidence for chronic IVIg, however the PBAC considered that there was no evidence to suggest superior efficacy or safety of zilucoplan versus chronic IVIg or PLEX.PSD · Mar 2025
Assumptions regarding changes in MG-ADL scores for Responders in the zilucoplan arm have larger improvements treatment responders were revised resulting in minor in MG-ADL scores than responders in the placebo arm which differences between treatment arms up to Week 12, and no was inconsistent with the clinical trial data (para 7.15). differences between treatment arms beyond Week 12.PSD · Mar 2025
The proportion of zilucoplan and placebo non-responders Non-responders in the treatment refractory setting switch to who receive IVIg/PLEX was revised (from 100% to 20%; with chronic IVIg/PLEX and escalated standard therapies and IVIg/PLEX patients receiving concomitant standard therapy), remain fully adherent for the remainder of the model, despite and a treatment effect associated with IVIg/PLEX therapy gaining no improvement in clinical outcomes with …PSD · Mar 2025
terms of safety compared to placebo in combination with standard therapy.PSD · Mar 2025
Source: Table 1.1-1, p4 of the resubmission Abbreviations: AChR, anti-acetylcholine receptor a The criteria for patients who were considered to be refractory to conventional immunotherapies are as follows: (1) treatment for at least 1 year with 2 or more of the following therapies: prednisone, azathioprine, mycophenolate, ciclosporin, cyclophosphamide, methotrexate, tacrolimus, rituximab, eculizumab, other corticosteroids for generalised myasthenia …PSD · Mar 2025
6.2 The PBAC noted and welcomed the input from individuals (15), health care professionals (10 individual health care professionals plus a group of 11 neurologists) and an organisation (Myasthenia Alliance Australia (MAA)) via the Consumer Comments facility on the PBS website. The comments described the high unmet need for new therapies to treat gMG.PSD · Mar 2025
6.3 The comments noted the efficacy associated with zilucoplan and the rapid onset of action. The comments noted the ease of administration of zilucoplan given it is a self- administered daily subcutaneous injection, which would provide flexibility for patients. The input outlined the risk of infection associated with zilucoplan including the risk of meningococcal infection.PSD · Mar 2025
Cost-effectiveness
ICER values are redacted/commercially sensitive. The document indicates an estimated ICER of $ 1 per QALY gained (within ranges $355,000 to <$455,000 or $255,000 to <$355,000) but exact values are not published.
Decision context
PopulationAdult patients (≥18 years) with symptomatic generalised myasthenia gravis who are AChR-antibody positive and refractory to conventional immunotherapies (defined as treatment for ≥1 year with ≥2 of specified therapies, or history of ≥1 year of specified therapy plus requirement for chronic PLEX/IVIg/subcutaneous immunoglobulin ≥every 3 months), receiving concomitant standard therapy (anticholinesterases, corticosteroids, and/or immunosuppressive agents).
Risk sharingThe sponsor proposed an RSA (risk sharing arrangement) based on the financial estimates of the resubmission, with no further details provided.
Why it was knocked back
- limitations of the economic evaluation, high price (driver of ICER), inadequate restriction criteria (not requiring optimisation of corticosteroid/immunosuppressive therapy or timeframe for assessing response), continuation criterion based on 3-point MG-ADL reduction (46.1% of placebo group achieved this by placebo effect alone), absence of stopping rules, inadequate safety data despite meningococcal infection risk requiring vaccination, overestimated assumptions regarding IVIg/PLEX cost offsets and clinical event rates
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2025 | Recommended · restricted | placebo | — | RCT · Other |
| Jul 2024 | Not recommended | placebo | — | RCT · Surrogate |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| RAISE | Ph 3 | 174 | Change From Baseline (CFB) to Week 12 in Myasthenia Gravis-Activities of Daily Living (MG-… | completed |
Consumer voice
Consumer input from 15 individuals, 10 healthcare professionals, 11 neurologists, and Myasthenia Alliance Australia described the significant unmet need for gMG treatments, highlighting impacts on quality of life, work and social participation, and the burden of current treatments. Contributors expressed enthusiasm for zilucoplan due to its efficacy and ease of administration, though acknowledged
believe this drug is being considered for those with refractory or severe disease only. However, its rapid onset of action gives clinicians the opportunity to gain rapid control of this condition in the acute setting, regardless of refractoriness. Rapid control in this condition is important to minimise side effects from other treatments as outlined above, reduce hospital length of stay, minimise utility of an infusion centre, and prevent disease progression…. I believe there should be a mechanism for appropriate patients to access early treatment. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to patients refractory to conventional immunotherapies with ≥1 year prior treatment; TGA label includes all AChR-antibody positive gMG adults.