Zilucoplan

RA101495, Zilbrysq

Immune & bioregulators

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Zilucoplan is an approved prescription medicine for generalised myasthenia gravis. This page explains the published science. Community or self-directed use is essentially none documented.

1What it is

Zilucoplan is the first peptide-based complement C5 inhibitor and the first self-injected treatment of its kind for myasthenia gravis. It was discovered through mRNA-display screening of very large cyclic-peptide libraries and optimised to bind C5 tightly. A fatty-acid tail lets it ride on albumin so a small peptide achieves a of about a week.

Generalised myasthenia gravis is an autoimmune disease in which antibodies, most often against the acetylcholine receptor, trigger complement attack on the muscle side of the nerve-muscle junction. Zilucoplan is approved for adults who are positive for those antibodies. It was approved by the FDA in October 2023, the EMA and MHRA in late 2023, and the TGA in Australia in August 2024.

2How it's thought to work

Zilucoplan binds C5 with high affinity at a site that blocks its cleavage by the C5 convertase, and at a second site on the C5b fragment that blocks assembly with C6, giving a dual mechanism.

Because it acts downstream of C3, it leaves the opsonising and immune-clearance functions of C3 intact, which is thought to carry a lower infection risk than C3 inhibition (compare pegcetacoplan, profile #223).

Daily dosing produces rapid (within hours) and sustained near-complete inhibition of complement activity.

A macrocyclic peptide blocking complement at C5, both its cleavage and the assembly that follows. Because it acts below C3, the opsonising functions of C3 are left intact.Schematic — not to scale

3What the research shows

Generalised myasthenia gravis (AChR-antibody positive)

RAISE randomised 174 adults to zilucoplan 0.3 mg/kg daily or placebo for 12 weeks. The MG-ADL score (a patient-reported daily-activity scale) improved by 4.39 points versus 2.30 with placebo, a difference of about 2.1 points; the clinician-rated QMG score improved by about 2.9 points more than placebo. Benefit was apparent by week 1 (Howard 2023, Lancet Neurol). The open-label extension RAISE-XT reported sustained benefit and no new safety signals over more than a year (Weiss 2024, Ther Adv Neurol Disord †). [1][3]

Graded A (small)

Earlier Phase 2

A 44-patient Phase 2 trial showed dose-dependent improvement in QMG and MG-ADL over 12 weeks (Howard 2020, JAMA Neurol). [2]

Graded B/negative

Other complement-mediated diseases

Studied in immune-mediated necrotising myopathy (Phase 2 did not meet its endpoint), PNH and severe COVID-19 (no clear benefit) †.

4Reported side effects and interactions

Literature-reported

Injection-site bruising (around 16%), upper respiratory infection, diarrhoea, headache. Lipase and amylase elevations were seen in some patients and pancreatitis occurred in a few; the label advises monitoring. Boxed warning: increased risk of meningococcal infection, as with all C5 inhibitors; vaccination against meningococcal disease (serogroups A, C, W, Y and B) is required at least two weeks before starting, and in the US a REMS programme applies. Serious infections and pancreatitis are the key risks.

Community-reported

none documented.

Theoretical. anti-drug antibodies were infrequent and not clinically significant in trials.

Interactions. no pharmacokinetic interactions established. Co-use with other complement inhibitors is not studied.

Markers researchers commonly monitor

Per label and trial protocols:

Marker	Why it's watched
Serum lipase and amylase	the label recommends baseline and periodic checks because of pancreatitis cases.
MG-ADL and QMG scores	the clinical efficacy measures.
Meningococcal vaccination status and fever vigilance	the central safety requirement for any C5 inhibitor.
Complement activity (CH50 or sheep red-cell haemolysis assay)	research measure of pharmacodynamic effect; not routine clinically.
Liver enzymes	monitored in trials; no major signal.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Supplied as ready-to-use pre-filled syringes in three fixed strengths; no . Patients are trained to self-inject into the abdomen, thigh or upper arm, rotating sites. The calculator does not apply.

6Commonly studied alongside

Used as an add-on to standard therapies (pyridostigmine, corticosteroids, azathioprine, mycophenolate) in RAISE. Comparator C5 inhibitors (eculizumab, ravulizumab) are monoclonal antibodies, not peptides. Related peptide complement inhibitor: pegcetacoplan (#223).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved October 2023 (Zilbrysq) for AChR-antibody-positive generalised myasthenia gravis in adults; REMS applies
European Union	EMA-authorised December 2023 †
United Kingdom	MHRA-licensed late 2023; NICE guidance published 2024–2025 †
Australia	TGA-registered August 2024 (ARTG entry 20 August 2024); Black Triangle Scheme
South Africa	Not registered †
Sport (WADA)	Not on the Prohibited List

8Open questions

Long-term infection risk with years of daily C5 blockade outside trial populations.
Whether zilucoplan benefits patients without AChR antibodies (MuSK-positive or seronegative), who were excluded from RAISE.
Head-to-head efficacy versus antibody C5 inhibitors and the newer FcRn blockers; only indirect comparisons exist.

9References

1Howard JF Jr 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 Neurol. PubMed · DOI
2Howard JF Jr et al. (2020). 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. PubMed · DOI
3Weiss MD et al. (2024). Zilucoplan long-term safety and efficacy in generalised myasthenia gravis: interim results of the open-label extension RAISE-XT. Ther Adv Neurol Disord [verify]. PubMed
4Ricardo A et al. (2015). Development of RA101348, a potent cyclic peptide inhibitor of C5 for complement-mediated diseases. Blood (abstract) [verify]. DOI
5Zilbrysq US prescribing information (2023, current); EMA Zilbrysq EPAR; TGA AusPAR for Zilbrysq (2024). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

31 Oct 2026Profile published — awaiting medical review

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