Zilucoplan

FDA-approved complement C5 inhibitor (macrocyclic peptide)Established

Also known as: Zilbrysq, RA101495

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.

Calculate Dose

For research use only.

Key Facts

CAS: 1841136-73-9
Molecular Weight (MW): 3562.23 g/mol
Half-life: About 172 hours (7 to 8 days)
FDA status: Approved
Evidence level: FDA Approved
Human dose established: Yes
Administration Route: Subcutaneous
Frequency: Once daily
Last updated: Oct 30, 2026
Reviewed: Oct 30, 2026
Targets: Complement C5

Research summary

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.

Research evidence

Regulatory review (FDA label)1 reviewed source
Controlled human trials5 reviewed sources
Early or uncontrolled human studies1 reviewed source
Lab & animal studies1 reviewed source

How it works

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.

Peptide Library's Zilucoplan profile summarises 6 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.

Zilucoplan dosage evidence

Zilucoplan has an FDA-approved human dosage. As Zilbrysq it is a once-daily subcutaneous injection set by body weight: 16.6 mg under 56 kg, 23 mg from 56 kg to under 77 kg, and 32.4 mg at 77 kg and above, for adults with generalized myasthenia gravis who are anti-acetylcholine receptor antibody positive. It carries a boxed warning for meningococcal infection and is available only through a REMS program.

FDA Approved

Dosage evidence summary for Zilucoplan
Human dosing established	Yes
Studied dose range	16.6–32.4 mg once daily, by body weight
Route	Subcutaneous
Frequency	Once daily
Duration studied	Continuous
Titration	None. The dose is fixed by weight band. Before the first dose, the label requires meningococcal vaccination at least 2 weeks ahead (unless delay is riskier than the infection) and baseline lipase and amylase levels.
Half-life	About 172 hours (7 to 8 days)
Evidence level	FDA Approved
Last reviewed	2026-10-30

Research-reported dosing

Doses as studied, one row per regimen. Different trials used different regimens; they are listed separately rather than averaged.

Research-reported dosing for Zilucoplan, one row per studied regimen
Study / context	Population	Dose	Route	Frequency	Duration	Outcome studied	Source
FDA label — Zilbrysq (revised October 2026)FDA-approved label · FDA prescribing information	Adults with generalized myasthenia gravis who are anti-acetylcholine receptor antibody positive	16.6 mg under 56 kg; 23 mg at 56 to under 77 kg; 32.4 mg at 77 kg and above	Subcutaneous, by prefilled syringe or autoinjector	Once daily	Continuous	Improvement in myasthenia gravis symptoms	ZILBRYSQ (zilucoplan) injection — FDA prescribing information, revised 10/2026 (Drugs@FDA)
Howard et al., 2023 — RAISE, phase 3Clinical trial · Randomised, double-blind, placebo-controlled phase 3	Adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (86 on zilucoplan, 88 on placebo)	0.3 mg/kg	Subcutaneous self-injection	Once daily	12 weeks	MG-ADL score improved by 4.39 points versus 2.30 on placebo	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.
Howard et al., 2020 — phase 2Clinical trial · Randomised, double-blind, placebo-controlled phase 2	Adults with moderate to severe generalized myasthenia gravis (n=44)	0.1 or 0.3 mg/kg	Subcutaneous self-injection	Once daily	12 weeks	QMG and MG-ADL scores improved at 0.3 mg/kg; the 0.1 mg/kg effect was slower and smaller	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.
Howard et al., 2024 — RAISE-XT, open-label extension (interim)Clinical trial · Open-label phase 3 extension, interim analysis	Patients from the phase 2 and phase 3 trials (n=200; median exposure 1.2 years)	0.3 mg/kg	Subcutaneous self-injection	Once daily	Ongoing at the interim analysis, up to 4.45 years	MG-ADL improvements held through week 60; 94% had an adverse event, most often worsening myasthenia gravis or COVID-19	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.
Paganoni et al., 2025 — HEALEY ALS Platform Trial (not an approved use)Clinical trial · Randomised, double-blind, placebo-controlled phase 2/3 platform trial	People with amyotrophic lateral sclerosis (122 on zilucoplan, 40 on matching placebo)	0.3 mg/kg	Subcutaneous	Once daily	Planned 24 weeks	Stopped early for futility; no change in disease progression	Paganoni S et al. Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Netw Open. 2025.
Mammen et al., 2023 — immune-mediated necrotizing myopathy, phase 2 (not an approved use)Clinical trial · Randomised, double-blind, placebo-controlled phase 2	Adults with anti-HMGCR or anti-SRP antibody-positive myopathy (12 on zilucoplan, 15 on placebo)	0.3 mg/kg	Subcutaneous	Once daily	8 weeks	No meaningful difference from placebo in creatine kinase; the study was terminated	Mammen AL et al. Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial. Lancet Rheumatol. 2023.
NCT03078582 — PNH, phase 2 (not an approved use)Clinical trial · Phase 2 trial with posted results	Patients with paroxysmal nocturnal hemoglobinuria (n=26), treatment-naive or previously on eculizumab	0.3 mg/kg on day 1, then 0.1 mg/kg daily to start	Subcutaneous	Once daily	—	Results posted on the registry	NCT03078582 — Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495) to Treat PNH Patients

Preclinical and analog research

Not human dosing evidence. Listed for completeness and never extrapolated to a human dose.

Research-reported dosing for Zilucoplan, one row per studied regimen
Study / context	Population	Dose	Route	Frequency	Duration	Outcome studied	Source
Preclinical — animal reproduction studyPreclinical · Animal toxicology reported in the FDA label	Pregnant monkeys	1, 2 or 4 mg/kg/day; not convertible to a human dose	Subcutaneous	Daily through gestation	—	More embryofetal deaths at all doses, with no maternal toxicity; no no-effect dose was identified	ZILBRYSQ (zilucoplan) injection — FDA prescribing information, section 8.1 (Drugs@FDA)

Where sources disagree

The trials dosed zilucoplan at 0.3 mg/kg. The label turns that into three fixed weight bands, so the labeled dose in mg/kg varies a little within each band.
The label is limited to adults who are anti-AChR antibody positive. Trials in ALS and immune-mediated necrotizing myopathy found no benefit, and safety and effectiveness have not been established in children.
DailyMed's copy of the label predated the October 2026 FDA revision at this review. That revision added the autoinjector and left the dose unchanged.
RAISE was 12 weeks long. Longer-term signals come from open-label extensions: pancreatitis or pancreatic cysts in 3.3% of patients, and morphea in 5%, usually after more than a year.

Zilucoplan dosage in published studies and labels →

Handling & administration

Reconstitution Guide: No reconstitution: supplied ready to use in a prefilled syringe or autoinjector
Injection Sites: AbdomenThighsBack of upper arms

Sequence & molecular data

Sequence and molecular data for Zilucoplan
Amino acid 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	3562.23 g/mol
CAS number	1841136-73-9
Half-life	About 172 hours (7 to 8 days)
Appearance	Clear to slightly opalescent, colorless solution in prefilled syringes or autoinjectors
Formulation	Solution
PubChem CID	133083018
FDA UNII	YG391PK0CC
ChEMBL	CHEMBL4298207
DrugBank	DB15636

Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.

Science

Mechanism of Action

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.

Origin

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

Targets

Complement C5

Studies

Research statistics

62 PubMed publications · 43.1% human clinical research · 19 registered trials

Counts of published research through 2026-11-01, not evidence that it works. Publications by year, study types and trials · How publications are counted

Regulatory & research 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.

Regulatory and research status for Zilucoplan
FDA status	Approved
Research status	Approved product (see FDA status)
Availability	Prescription-Only
WADA (sport)	Unknown / Not Listed
Library classification	FDA-Approved

How FDA approval, compounding and research-only status differ

Benefits

MG-ADL score improved by 4.39 points versus 2.30 on placebo at week 12 (RAISE)73.1% had at least a 3-point MG-ADL improvement at week 12, versus 46.1% on placeboQMG muscle weakness score improved by 6.19 points versus 3.25 on placeboImprovements held through week 60 in an open-label extension

Zilucoplan side effects

The effects below are drawn from Zilucoplan's prescribing information, which lists the full adverse-reaction data.

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%)

Contraindications

Starting treatment with an unresolved serious Neisseria meningitidis infection

Storage & stability

This compound is not supplied as a powder to be mixed, so the freeze-dried powder and reconstitution handling described for research peptides does not apply. Storage conditions are product-specific: follow the label or packaging of the product itself.

Zilucoplan: 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.

Is zilucoplan FDA approved?

Yes. FDA approved zilucoplan as Zilbrysq on 17 October 2023 (NDA 216834, UCB) for adults with generalized myasthenia gravis who are anti-acetylcholine receptor antibody positive. An October 2026 supplement added a prefilled autoinjector to the prefilled syringe.

What is the labeled dose of zilucoplan?

The FDA label sets the once-daily subcutaneous dose by body weight: 16.6 mg under 56 kg, 23 mg from 56 kg to under 77 kg, and 32.4 mg at 77 kg and above. The trials dosed 0.3 mg/kg. This is reference information, not medical advice.

What are the side effects of zilucoplan?

In the 12-week phase 3 trial, the most common were injection site reactions (29% versus 16% on placebo), upper respiratory tract infections (14% versus 7%) and diarrhea (11% versus 2%). The label has a boxed warning for meningococcal infection and warns about pancreatitis. This is reference information, not medical advice.

Why does zilucoplan have a boxed warning?

Blocking terminal complement raises the risk of serious infection with Neisseria meningitidis, even after vaccination. The label calls for meningococcal vaccination at least 2 weeks before the first dose unless delay is riskier, and the drug is available only through a REMS program.

What is the half-life of zilucoplan?

The label gives a mean terminal half-life of about 172 hours, or 7 to 8 days. Zilucoplan is more than 99% bound to plasma proteins, and steady-state trough levels were reached by week 4 of daily dosing.

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
External reference
ZILBRYSQ (zilucoplan) injection — DailyMed
External reference
Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE) — Lancet Neurol, 2023
External reference
Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis — JAMA Neurol, 2020
External reference
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
External reference
Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis — JAMA Netw Open, 2025
External reference
Zilucoplan in immune-mediated necrotising myopathy — Lancet Rheumatol, 2023
External reference
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
External reference
NCT04115293 — RAISE phase 3 trial of zilucoplan
External reference

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Compiled by Peptide Library Editorial · Reviewed Oct 30, 2026 · Updated Oct 30, 2026 · Version 1

This Zilucoplan profile is compiled from published literature (6 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error

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