Page data last changed: . Chemistry registry snapshot: . Registry refreshes and identity assessments are separate from scientific content review.
A self-injected macrocyclic peptide that does what the antibody eculizumab does — block C5 — in a daily subcutaneous dose.
Also known as: RA101495 · RA 101495 · Zilbrysq (brand)
Part of the Neuropeptides & signaling cluster
Overview
Zilucoplan (Zilbrysq) is a synthetic macrocyclic peptide that binds complement C5 and blocks its cleavage, preventing formation of the membrane attack complex. Approved in 2023 in Japan, the US and the EU for AChR-antibody-positive generalised myasthenia gravis, it is self-administered subcutaneously once daily; in the phase 3 RAISE trial it improved the MG-ADL score by 4.39 points versus 2.30 with placebo at 12 weeks.
Source & context
Biological / chemical source: Synthetic macrocyclic peptide developed by Ra Pharmaceuticals, later UCB
Primary research or clinical context: Approved (Japan September 2023; FDA October 2023; EMA December 2023) for acetylcholine-receptor-antibody-positive generalised myasthenia gravis
What zilucoplan is
Zilucoplan (RA101495) is a synthetic, macrocyclic peptide that blocks the cleavage of complement C5 into C5a and C5b, which occurs as a consequence of activation of the classical, alternative or lectin pathways; blocking that step inhibits formation of the membrane attack complex (IUPHAR ligand 10404). It was developed by Ra Pharmaceuticals for tissue-based complement-mediated disorders and progressed in paroxysmal nocturnal haemoglobinuria and generalised myasthenia gravis (gMG). The earliest approval for gMG was issued in Japan in September 2023, with FDA approval in October and EMA authorisation in December (IUPHAR clinical-use record; Shirley, Drugs 2024).
Mechanism
In AChR-antibody-positive myasthenia gravis, autoantibodies at the neuromuscular junction activate complement, and the resulting membrane attack complex damages the post-synaptic membrane. Zilucoplan intercepts the cascade at C5, the same step targeted by the monoclonal antibodies eculizumab and ravulizumab, but as a small peptide that patients inject themselves rather than an infused antibody. Its molecular formula is C172H278N24O55 with an average mass of about 3,562 Da (PubChem CID 133083018).
Clinical evidence: RAISE
RAISE was a randomised, double-blind, placebo-controlled phase 3 trial at 75 sites in Europe, Japan and North America in adults with AChR-positive gMG. Of 174 patients, 86 received zilucoplan 0.3 mg/kg and 88 placebo. Zilucoplan produced a greater reduction in the MG-ADL score from baseline to week 12 (least-squares mean change −4.39 vs −2.30; difference −2.09; p=0.0004). Treatment-emergent adverse events occurred in 77% versus 70%, the most common being injection-site bruising (16% vs 9%); serious adverse events and serious infections were similar between groups (Howard et al., Lancet Neurology 2023). An earlier phase 2 trial in 44 patients had shown clinical effects (Howard et al., JAMA Neurology 2020).
| Endpoint | Zilucoplan 0.3 mg/kg | Placebo |
|---|---|---|
| MG-ADL change from baseline | −4.39 | −2.30 |
| Any treatment-emergent adverse event | 77% | 70% |
| Injection-site bruising | 16% | 9% |
Long-term data
In the open-label extension RAISE-XT, patients who completed a qualifying study self-administered daily subcutaneous zilucoplan 0.3 mg/kg; interim analysis assessed long-term safety and efficacy (Howard et al., Therapeutic Advances in Neurological Disorders 2024), fatigue improved on the Neuro-QoL scale (Weiss et al., Journal of Neurology 2024), and corticosteroid and immunosuppressant doses could be changed at investigators' discretion after the first 12 weeks (Hewamadduma et al., Journal of Neurology 2025).
Other indications
Zilucoplan was tested in amyotrophic lateral sclerosis as regimen A of the HEALEY ALS platform trial, with 162 participants randomised 3:1 to zilucoplan or placebo (Paganoni et al., JAMA Network Open 2025), and was included in the UK's ACCORD initiative evaluating candidate COVID-19 treatments in 2020 (IUPHAR record). ClinicalTrials.gov lists 19 studies as of September 2026, including paediatric gMG trials (NCT06055959, NCT06435312), a trial in severe gMG exacerbations (NCT07215949) and a lactation study (NCT06961747). The lactation database expects it to be degraded to small peptides in the infant gut (LactMed).
What this page is not
Zilucoplan is a prescription medicine for a rare autoimmune disease; this profile explains its chemistry and evidence for educational purposes and is not treatment guidance. It is included in the directory as an example of a macrocyclic peptide replacing an antibody at the same molecular target.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Synthetic macrocyclic peptide; self-administered subcutaneously once daily at 0.3 mg/kg in trials
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C172H278N24O55
- Average reference mass
- ≈ 3,562
- Receptors
- Complement component C5 (binds C5 and blocks cleavage to C5a and C5b) — not a receptor ligand
- Backbone
- Synthetic macrocyclic peptide; self-administered subcutaneously once daily at 0.3 mg/kg in trials
- Status
- Approved: Japan (September 2023), FDA (October 2023), EMA (December 2023) for AChR+ generalised myasthenia gravis; under review in Australia and Canada at first-approval publication
- PubChem CID: 133083018
- IUPHAR ligand: 10404
- CAS RN: 1841136-73-9
- UNII: YG391PK0CC
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 19 registered studies with “Zilucoplan” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT07215949 | Zilucoplan for Severe gMG Exacerbations | Phase 3 | recruiting | 2026-08-28 |
| NCT06961747 | A Study to Assess Zilucoplan Concentration in Breast Milk of Healthy Lactating Women | Phase 1 | recruiting | 2026-08-27 |
| NCT04225871 | Open-Label Extension of Zilucoplan in Subjects With Generalized Myasthenia Gravis | Phase 3 | completed | 2026-08-12 |
| NCT06055959 | A Study to Evaluate Subcutaneous Zilucoplan in Pediatric Participants With Generalized Myasthenia Gravis | Phase 3 | recruiting | 2026-07-31 |
| NCT06435312 | An Open-label Extension Study to Evaluate Subcutaneous Zilucoplan in Pediatric Participants With Generalized M | Phase 3 | enrolling by invitation | 2026-07-31 |
| NCT04297683 | HEALEY ALS Platform Trial - Master Protocol | Phase 3 | active not recruiting | 2026-07-21 |
Zilucoplan — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Synthetic macrocyclic peptide; self-administered subcutaneously once daily at 0.3 mg/kg in trialsAverage reference mass: 3,562 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- IdentifiersCross-linked to IUPHAR ligand 10404 and PubChem CID 133083018.
- TrialsClinicalTrials.gov snapshot added: 19 registered studies, highest phase 3.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Zilucoplan
What is Zilucoplan?+
Zilucoplan (Zilbrysq) is a synthetic macrocyclic peptide that binds complement C5 and blocks its cleavage, preventing formation of the membrane attack complex. Approved in 2023 in Japan, the US and the EU for AChR-antibody-positive generalised myasthenia gravis, it is self-administered subcutaneously once daily; in the phase 3 RAISE trial it improved the MG-ADL score by 4.39 points versus 2.30 with placebo at 12 weeks.
What Canadian product status is recorded for Zilucoplan?+
Canadian product status for Zilucoplan has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Zilucoplan?+
Zilucoplan is not a classic amino-acid chain peptide in the same sense; see the profile for classification details.
What is zilucoplan?+
A synthetic macrocyclic peptide that binds complement C5 and blocks its cleavage, preventing membrane attack complex formation. Sold as Zilbrysq, it is approved for AChR-antibody-positive generalised myasthenia gravis.
Is zilucoplan approved?+
Yes: Japan (September 2023), FDA (October 2023) and EMA (December 2023) for generalised myasthenia gravis.
How is zilucoplan given?+
As a once-daily subcutaneous self-injection at 0.3 mg/kg in the trials — unlike C5 antibodies, which are infused.
How effective was zilucoplan in RAISE?+
MG-ADL score fell by 4.39 points versus 2.30 with placebo at 12 weeks (difference −2.09, p=0.0004).
Related peptides
References & further reading
- 1.Howard et al. (2023). Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurology
- 2.Shirley (2024). Zilucoplan: First Approval. Drugs
- 3.Howard et al. (2020). Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis. JAMA Neurology
- 4.Howard et al. (2024). Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study. Therapeutic Advances in Neurological Disorders
- 5.Paganoni et al. (2025). Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Network Open
- 6.PubChem — compound summary for Zilucoplan (CID 133083018)