---
title: "Zilucoplan"
canonical_url: https://peptidelibrary.app/library/zilucoplan
description: "FDA-approved macrocyclic peptide (Zilbrysq) that inhibits complement C5, for adults with generalized myasthenia gravis who are anti-acetylcholine receptor antibody positive. A daily self-injection with a boxed warning for meningococcal infection."
updated: 2026-10-30
publisher: Peptide Library
notice: "Research and educational use only. Not medical advice."
---

# Zilucoplan

Zilucoplan (also called Zilbrysq or RA101495) is an FDA-approved complement C5 inhibitor (macrocyclic peptide). Zilucoplan binds complement protein C5 and stops it being cleaved into C5a and C5b, which prevents assembly of the terminal complement complex, C5b-9. In lab studies it also interfered with C5b6 formation and kept working against C5 variants at R885 that respond poorly to eculizumab.

FDA-approved macrocyclic peptide (Zilbrysq) that inhibits complement C5, for adults with generalized myasthenia gravis who are anti-acetylcholine receptor antibody positive. A daily self-injection with a boxed warning for meningococcal infection.

Also known as: Zilbrysq, RA101495.

## Classification

- Type: FDA-approved complement C5 inhibitor (macrocyclic peptide)
- Mechanism class: Complement C5 Inhibitor
- Development stage: Approved product
- Regulatory class: FDA-approved medicine

## Mechanism

Zilucoplan binds complement protein C5 and stops it being cleaved into C5a and C5b, which prevents assembly of the terminal complement complex, C5b-9. In lab studies it also interfered with C5b6 formation and kept working against C5 variants at R885 that respond poorly to eculizumab. The label says its exact mechanism in generalized myasthenia gravis is unknown but presumed to involve less C5b-9 deposition at the neuromuscular junction.

Targets: Complement C5.

Origin: Synthetic macrocyclic peptide developed by Ra Pharmaceuticals as RA101495, now part of UCB.

## Properties

- Sequence: Ac-[Lys-Val-Glu-Arg-Phe-Asp]-(N-Me)Asp-tLeu-Tyr-7-azaTrp-Glu-Tyr-Pro-cyclohexylGly-Lys(Nε-palmitoyl-γ-Glu-PEG24), with a lactam ring between residues 1 and 6
- Molecular formula: C172H278N24O55
- Molecular weight: 3,562.23 g/mol
- CAS number: 1841136-73-9
- Half-life: About 172 hours (7 to 8 days)
- Studied routes: Subcutaneous

## Evidence

- Evidence level: FDA Approved
- Highest documented: Regulatory review (FDA label)
- Human trials: 6
- Controlled human trials: 5
- Preclinical sources: 1
- Latest source: 2026

Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.

### Studies

1. ZILBRYSQ (zilucoplan) injection — FDA prescribing information, revised 10/2026 (Drugs@FDA). 2026. Regulatory label (FDA), human. Population: Adults with generalized myasthenia gravis who are anti-acetylcholine receptor antibody positive. Improvement in myasthenia gravis symptoms [Source](https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/216834s015lbl.pdf)
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. 2023. Controlled human trial. Population: Adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (86 on zilucoplan, 88 on placebo). MG-ADL score improved by 4.39 points versus 2.30 on placebo [Source](https://pubmed.ncbi.nlm.nih.gov/37059508/)
3. Howard JF Jr et al. Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis: Results of a Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial. JAMA Neurol. 2020. 2020. Controlled human trial. Population: Adults with moderate to severe generalized myasthenia gravis (n=44) [Source](https://pubmed.ncbi.nlm.nih.gov/32065623/)
4. Howard JF Jr et al. Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study. Ther Adv Neurol Disord. 2024. 2024. Controlled human trial. Population: Patients from the phase 2 and phase 3 trials (n=200; median exposure 1.2 years). MG-ADL improvements held through week 60; 94% had an adverse event, most often worsening myasthenia gravis or COVID-19 [Source](https://pubmed.ncbi.nlm.nih.gov/38638673/)
5. Paganoni S et al. Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Netw Open. 2025. 2025. Controlled human trial. Population: People with amyotrophic lateral sclerosis (122 on zilucoplan, 40 on matching placebo). Stopped early for futility; no change in disease progression [Source](https://pubmed.ncbi.nlm.nih.gov/39960672/)
6. Mammen AL et al. Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial. Lancet Rheumatol. 2023. 2023. Controlled human trial. Population: Adults with anti-HMGCR or anti-SRP antibody-positive myopathy (12 on zilucoplan, 15 on placebo). No meaningful difference from placebo in creatine kinase; the study was terminated [Source](https://pubmed.ncbi.nlm.nih.gov/36923454/)
7. NCT03078582 — Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495) to Treat PNH Patients. Human study (early or uncontrolled). Population: Patients with paroxysmal nocturnal hemoglobinuria (n=26), treatment-naive or previously on eculizumab. Results posted on the registry [Source](https://clinicaltrials.gov/study/NCT03078582)
8. ZILBRYSQ (zilucoplan) injection — FDA prescribing information, section 8.1 (Drugs@FDA). Preclinical: animal or lab study. Population: Pregnant monkeys. More embryofetal deaths at all doses, with no maternal toxicity; no no-effect dose was identified. Limitations: Lab or animal research: not evidence of a human effect or dose. [Source](https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/216834s015lbl.pdf)

### Registered trials

- [NCT03078582](https://clinicaltrials.gov/study/NCT03078582)

## Safety

Side effects: Injection site reactions (29% versus 16% on placebo); Upper respiratory tract infections (14% versus 7%); Diarrhea (11% versus 2%); Urinary tract infection (8% versus 5%); Increased lipase (7% versus 0%) and amylase (5% versus 1%).

Risks: Boxed warning: serious, life-threatening meningococcal infections; vaccination at least 2 weeks before the first dose and a REMS program are required; Other serious infections, including disseminated gonococcal infection; Pancreatitis and pancreatic cysts (3.3% in open-label extensions); Morphea (5% in open-label extensions, usually after more than a year); May cause fetal harm based on monkey data; Safety and effectiveness not established in children.

Contraindications: Starting treatment with an unresolved serious Neisseria meningitidis infection.

Human safety basis: FDA prescribing information

## Regulatory status

Zilucoplan is an FDA-approved product for specific labelled indications. Approval does not extend to the research contexts described on this page, and approved products are prescription medicines.

- FDA status: Approved
- Availability: Prescription-Only

## Frequently asked questions

### What is zilucoplan?

Zilucoplan is a once-daily self-injected medicine sold as Zilbrysq for generalized myasthenia gravis, an autoimmune disease that weakens muscles. It is a 15-amino-acid synthetic macrocyclic peptide, approved by FDA in October 2023 for adults with anti-acetylcholine receptor antibodies.

### How does zilucoplan work?

Zilucoplan binds complement protein C5 and stops it splitting into C5a and C5b, which blocks the final complement complex, C5b-9. In myasthenia gravis, that complex is presumed to damage the junction between nerve and muscle, though the label says the exact mechanism is unknown.

### What compounds are similar to zilucoplan?

Pegcetacoplan is the closest relative in this library, also a peptide complement inhibitor but acting at C3 rather than C5. Enlicitide is another macrocyclic peptide with an unrelated target. Their uses and risks differ.

## References

- [ZILBRYSQ (zilucoplan) injection — FDA prescribing information, revised 10/2026](https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/216834s015lbl.pdf)
- [ZILBRYSQ (zilucoplan) injection — DailyMed](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f1d53d6-e495-4a3a-8bb9-680a15d25034)
- [Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE) — Lancet Neurol, 2023](https://pubmed.ncbi.nlm.nih.gov/37059508/)
- [Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis — JAMA Neurol, 2020](https://pubmed.ncbi.nlm.nih.gov/32065623/)
- [Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study — Ther Adv Neurol Disord, 2024](https://pubmed.ncbi.nlm.nih.gov/38638673/)
- [Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis — JAMA Netw Open, 2025](https://pubmed.ncbi.nlm.nih.gov/39960672/)
- [Zilucoplan in immune-mediated necrotising myopathy — Lancet Rheumatol, 2023](https://pubmed.ncbi.nlm.nih.gov/36923454/)
- [Zilucoplan, a macrocyclic peptide inhibitor of human complement component 5, uses a dual mode of action to prevent terminal complement pathway activation — Front Immunol, 2023](https://pubmed.ncbi.nlm.nih.gov/37622108/)
- [NCT04115293 — RAISE phase 3 trial of zilucoplan](https://clinicaltrials.gov/study/NCT04115293)

Note: Dose figures are left out of this Markdown version. See the cited sources.