EC approves adult generalised Myasthenia gravis treatment

Posted on 6 December, 2023 - Myasthenia Gravis

UCB announces European Commission approval of ZILBRYSQ[®]▼ (zilucoplan) 

  • European approval of ZILBRYSQ® (zilucoplan) granted as an add-on to standard therapy for the treatment of generalised Myasthenia Gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody-positive1
  • Zilucoplan is the first once-daily subcutaneous, targeted C5 complement inhibitor for gMG.2 
  • Approval supported by pivotal Phase 3 RAISE study in gMG2 which demonstrated treatment with zilucoplan resulted in statistically significant improvements in MG-specific efficacy outcomes compared to placebo
  • European approval for zilucoplan follows approvals in U.S. and Japan earlier in 20233,4
  • Alongside rozanolixizumab, which was recently approved in U.S. and Japan for the treatment of gMG,4,5 and which has received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP),6 zilucoplan is part of UCB’s portfolio of two different medicines for gMG, each with a distinct mechanism of action and with potential to offer physicians new and additional treatment choices

4th December, 2023: UCB, a global biopharmaceutical company, today announced that the European Commission (EC) has granted a marketing authorisation for ZILBRYSQ® (zilucoplan) as an add-on to standard therapy for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody-positive.1 

Zilucoplan is the first once-daily subcutaneous (SC), targeted peptide inhibitor of complement component 5 (C5) inhibitor for gMG, and the only C5 inhibitor approved for self-administration by adult patients with AChR antibody-positive gMG.2 

As a C5 inhibitor, zilucoplan inhibits complement-mediated damage to the neuromuscular junction through its targeted dual mechanism of action.2 Benefits of SC self-injection can include reduced traveling time to and from hospitals, decreased interference with work obligations, and increased independence.2 

Unlike monoclonal antibody C5 inhibitors, as a peptide, zilucoplan can be used concomitantly with intravenous immunoglobulin and plasma exchange, without the need for supplemental dosing.2 

The EC approval of zilucoplan is supported by safety and efficacy data from the RAISE study (NCT04115293), published in The Lancet Neurology in May 2023.2 The RAISE study was a multi-centre, phase 3, randomised, double-blind, placebo-controlled study to assess the efficacy, safety profile, and tolerability of zilucoplan in adult patients with anti-acetylcholine receptor (AChR) antibody-positive gMG. Patients were randomised in a 1:1 ratio to receive daily subcutaneous (SC) injections of 0.3 mg/kg zilucoplan or placebo for 12 Weeks. The study demonstrated that zilucoplan delivered rapid, consistent, clinically meaningful and statistically significant improvements in different patient- and clinician-reported outcomes at week 12 in a broad population of adult patients with mild-to-severe anti-AChR antibody-positive gMG.2  

As included within the zilucoplan EU Summary of Product Characteristics, the most frequently reported adverse reactions were injection site reactions (injection site bruising (13.9%) and injection site pain (7.0%)) and upper respiratory tract infections (nasopharyngitis (5.2%), upper respiratory tract infection (3.5%) and sinusitis (3.5%)).1

European approval of zilucoplan follows approvals by the U.S. Food and Drug Administration (FDA) for the treatment of generalised myasthenia gravis (gMG) in adult patients who are AChR antibody-positive and by the Japanese Ministry of Health, Labour and Welfare (MHLW) for the treatment of gMG in adult patients who inadequately respond to steroids or other immunosuppressants.3,4

gMG is a rare, chronic, heterogeneous, unpredictable autoimmune disease characterised by dysfunction and damage at the neuromuscular junction (NMJ).7,8,9 Several factors are understood to be drivers of gMG disease pathology, including the complement cascade, immune cells and pathogenic Immunoglobulin G (IgG) autoantibodies10.

In AChR antibody-positive gMG, pathogenic AChR autoantibodies (IgG1 and IgG3) initiate the classical complement pathway, which, together with the alternative and lectin complement pathways, converge at C5, leading to MAC (membrane attack complex) deposition, damage to the NMJ, loss of AChRs and subsequent impaired synaptic transmission.9,11 Preventing MAC formation reduces damage to the post-synaptic membrane, reduces disruption of ionic channel conductance and helps to preserve neuromuscular transmission.11 

MG has a global prevalence of 100–350 cases per every 1 million people.8

Alongside approval of zilucoplan, UCB’s neonatal Fc receptor (FcRn) blocker rozanolixizumab recently received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) as an add-on to standard therapy for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody-positive.6 This follows approvals for rozanolixizumab in similar indications in the U.S. and Japan earlier this year,4,5 further strengthening UCB’s gMG portfolio and the company’s commitment to addressing the gMG community’s unmet needs.

The approval of zilucoplan from the EC is valid in all EU member states, as well as in the European Economic Area (EEA) countries Iceland, Liechtenstein, and Norway. 

UCB is committed to making zilucoplan available to patients as quickly as possible and anticipates European availability will commence in the first quarter of 2024.

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

References: 

  1. Zilucoplan EU SmPC https://www.ema.europa.eu/en. Accessed December 2023.
  2. Howard JF Jr, et al. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2023;22(5):395-406. 
  3. ZILBRYSQ® U.S. Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216834s000lbl.pdf. Accessed December 2023.
  4. Data on file: Japan MHLW, 25 September 2023.
  5. Rozanolixizumab-noli FDA approval. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761286s000lbl.pdf. Accessed December 2023.
  6. EMA CHMP rozanolixizumab positive opinion. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/rystiggo#opinion-section. Accessed December 2023.
  7. National Institute of Neurological Disorders and Stroke. 2022. Myasthenia Gravis Fact Sheet. https://www.ninds.nih.gov/myasthenia-gravis-fact-sheet. Accessed December 2023.
  8. Punga AR, et al. Epidemiology, diagnostics, and biomarkers of autoimmune neuromuscular junction disorders. Lancet Neurol. 2022;21(2):176-88.
  9. Howard JF Jr. Myasthenia gravis: The role of complement at the neuromuscular junction. Ann N Y Acad Sci. 2018;1412(1):113‒28. 
  10. Phillips WD, Vincent A. Pathogenesis of myasthenia gravis: Update on disease types, models, and mechanisms. F1000Res. 2016;5:F1000 Faculty Rev-1513.
  11. Mantegazza R, et al. Complement inhibition for the treatment of myasthenia gravis. Immunotargets Ther. 2020;9:317–31.
  12. US Food and Drug Administration. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=699319. Accessed October 2023.
  13. Myasthenia Gravis Foundation of America. MG Quick Facts. https://myasthenia.org/MG-Education/MG-Quick-Facts. Accessed December 2023.
  14. Juel VC, Massey JM. Myasthenia gravis. Orphanet J Rare Dis. 2007;2:44.
  15. Bril V, et al. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol. 2023;22(5):383-94.
  16. RYSTIGGO® U.S. Prescribing Information: https://www.ucb-usa.com/RYSTIGGO-prescribing-information.pdf. Accessed December 2023.