Immune & antimicrobial

Zilucoplan

Also called Zilbrysq, zilucoplan sodium

Zilucoplan (brand name Zilbrysq) is a once-daily injection under the skin for adults with generalized myasthenia gravis who test positive for antibodies against the acetylcholine receptor. It is a small ring-shaped peptide that blocks complement C5, part of the immune system that damages the nerve-muscle connection in this disease. Because blocking complement raises the risk of serious meningococcal infection, it carries a boxed warning and is only available through a special safety program.

FDA-approvedApproved by the FDA for at least one use after large human trials.

New · under editorial review. Added October 30, 2026 by our automated research, with every claim sourced. A person has not checked this page yet; treat it with extra care. How we research

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Illustrative chain. The exact sequence has not been published in a source we could verify.

At a glance

Type: Peptide
Size: 15 amino acids in a macrocycle, plus a PEG linker and a palmitoyl (fatty acid) tail
Formula: C172H278N24O55 (free acid)
Molecular weight: 3562.23 Da (free acid, FDA label)
CAS number: 1841136-73-9
Origin: Fully synthetic peptide discovered by Ra Pharmaceuticals with its ExtremeDiversity platform. The label's chemical name includes non-standard residues such as 7-azatryptophan, tert-leucine, cyclohexylglycine and N-methyl-aspartate, a lactam ring closure, and a palmitoyl group attached via a gamma-glutamyl and 24-unit PEG linker. Supplied as the tetrasodium salt. Formula and mass from the FDA label and PubChem; CAS from PubChem [1][5][11][12].
Evidence: FDA-approved
US FDA status: FDA-approved as Zilbrysq (UCB; NDA 216834, new molecular entity, orphan) on October 17, 2023 for adults with generalized myasthenia gravis who are anti-AChR antibody positive. Available only through a REMS. An autoinjector (new route of administration supplement, action date October 15, 2026) was approved in October 2026 ¹²⁸.

Overview

How it works

Established: zilucoplan binds complement protein C5 and stops it being cut into C5a and C5b, so the membrane attack complex (C5b-9) cannot form ¹. A review describes a second action: it also blocks C5b from binding C6 ⁵. In myasthenia gravis, the label presumes the benefit comes from less C5b-9 deposited at the neuromuscular junction ¹. In treated patients, complement activity was about 97.5% inhibited by the end of week 1; the drug is over 99% protein-bound and has a half-life of about 172 hours (7–8 days) ¹.

What research shows

RAISE (phase 3 human RCT, n=174 adults with AChR-antibody-positive generalized MG, 12 weeks): the MG-ADL daily-activities score improved by 4.39 points on zilucoplan vs 2.30 on placebo (difference −2.09, p=0.0004) ³.
RAISE, label analysis: the QMG muscle-strength score improved by 6.19 vs 3.25 points, and 73.1% vs 46.1% of patients improved by at least 3 MG-ADL points ¹.
RAISE-XT (open-label extension, n=200, median 1.2 years): MG-ADL improvement was maintained at week 60 (about −6.0 in those who started on zilucoplan and −6.5 in those switched from placebo) ⁴.
Phase 2 trial (human RCT, n=44, 12 weeks): 0.1 and 0.3 mg/kg daily both improved MG scores; the higher dose acted faster and was chosen for phase 3 ⁵.
HEALEY ALS Platform Trial (human RCT, n=162, 24 weeks): zilucoplan did not slow ALS progression and was stopped early for futility ¹⁰.
Autoinjector studies (company press release, not peer reviewed): a phase 1 study (n=14) showed bioequivalence to the prefilled syringe, and a phase 3b study (n=31) reported complete dose delivery in 99.8% of autoinjector uses ⁸.

Doses studied in people

Study or label	Dose used	Source
FDA label (adults with AChR-antibody-positive generalized MG)	Once daily subcutaneous, by body weight: 16.6 mg (under 56 kg), 23 mg (56 to under 77 kg), 32.4 mg (77 kg and above)	¹
RAISE phase 3 RCT (n=174, 12 weeks)	0.3 mg/kg once daily, subcutaneous, vs placebo	³
RAISE-XT open-label extension (n=200)	0.3 mg/kg once daily, subcutaneous	⁴
Phase 2 RCT in generalized MG (n=44, 12 weeks)	0.1 mg/kg or 0.3 mg/kg once daily, subcutaneous, vs placebo	⁵
HEALEY ALS Platform Trial, regimen A (n=162, 24 weeks)	0.3 mg/kg once daily, subcutaneous, vs placebo	¹⁰

Doses shown are from the FDA label and published trials only; they are reported, not recommended.

Read this first: these are the amounts given to participants in published studies or written on official prescribing labels, reported for reference. They are not recommendations. Trial doses were chosen for specific patients under medical supervision, and a dose that is safe in one person can be harmful in another.

Safety

Boxed warning (label): life-threatening and fatal meningococcal infections can occur. Meningococcal vaccination is required at least 2 weeks before the first dose unless delay is riskier, and vaccination does not remove the risk ¹.
Because of this risk, it is available only through the ZILBRYSQ REMS safety program, and patients carry a safety card during treatment and for 2 months afterward ¹.
Other infections (label): serious Neisseria infections including disseminated gonococcal infection, and higher risk from other encapsulated bacteria such as pneumococcus ¹.
Pancreatitis and pancreatic cysts (label): seen in 7 patients (3.3%) in open-label extension studies; lipase and amylase are checked before starting. In RAISE, lipase rose in 7% vs 0% and amylase in 5% vs 1% on placebo ¹.
Common side effects in RAISE (label, zilucoplan vs placebo): injection-site reactions 29% vs 16%, upper respiratory infections 14% vs 7%, diarrhea 11% vs 2% ¹.
Morphea (a patchy skin hardening) was reported in 10 of 213 patients (5%) in the extension study, usually after more than a year ¹. Temporary rises in eosinophils have been seen ¹.
In RAISE, one death occurred in each group (COVID-19 on zilucoplan, brain bleed on placebo); neither was judged drug-related ³. In RAISE-XT, 94% had a side effect over follow-up, most often MG worsening (26%) and COVID-19 (25%) ⁴.
Monkey studies showed embryo-fetal death at exposures similar to human doses; safety in children is not established ¹.

Report side effects of any drug or product to the FDA through MedWatch. For a possible poisoning in the US, call Poison Control at 1-800-222-1222.

Legal status

FDA: FDA-approved as Zilbrysq (UCB; NDA 216834, new molecular entity, orphan) on October 17, 2023 for adults with generalized myasthenia gravis who are anti-AChR antibody positive. Available only through a REMS. An autoinjector (new route of administration supplement, action date October 15, 2026) was approved in October 2026 ¹²⁸.
Compounding: No compounding-specific FDA action for zilucoplan was found in the sources reviewed.
Sports (WADA): Not named on the 2026 WADA Prohibited List; it is an approved medicine, so the S0 'non-approved substances' class does not apply ¹³.
Other: Japan (September 25, 2023, first approval worldwide): adults with generalized MG who respond inadequately to steroids or other immunosuppressants ⁵⁶. European Union (December 1, 2023): add-on to standard therapy in AChR-antibody-positive adults; its EU orphan designation was withdrawn at the company's request ⁷.

Rules change often. See Legal status of peptides for how these categories work.

Storage and stability

Label: refrigerate at 2–8°C in the carton and do not freeze; patients may keep it at up to 30°C for one period of up to 3 months ¹.

General lab handling, not instructions for personal use. See Storage and stability.

History

Zilucoplan was originated by Ra Pharmaceuticals ⁵. UCB completed its purchase of Ra Pharma on April 2, 2020, when the drug was in phase 3 for generalized myasthenia gravis and also being explored in immune-mediated necrotizing myopathy and ALS ⁹. The phase 3 RAISE trial was published in 2023 ³. Japan approved it first, on September 25, 2023 ⁶; the FDA approved Zilbrysq on October 17, 2023 ²; and the European Union authorised it on December 1, 2023 ⁷. The FDA approved a new route of administration supplement on October 15, 2026, which UCB announced the next day as an autoinjector for self-administration ²⁸. Development for ALS, immune-mediated necrotizing myopathy, COVID-19 and paroxysmal nocturnal hemoglobinuria was discontinued ⁵.

Common questions

Is zilucoplan FDA-approved?

Yes. The FDA approved it as Zilbrysq on October 17, 2023 for adults with generalized myasthenia gravis who are anti-AChR antibody positive ¹². It is also approved in Japan and the EU ⁶⁷.

What did the RAISE trial show?

In 174 adults, daily-living MG scores improved by about 4.4 points on zilucoplan vs 2.3 on placebo after 12 weeks ³. Benefits held up to 60 weeks in the open-label extension ⁴.

Why does it have a boxed warning?

Blocking complement C5 raises the risk of serious, sometimes fatal meningococcal infections, so vaccination is required and the drug is only available through a REMS safety program ¹.

What are the common side effects?

In RAISE, injection-site reactions, upper respiratory infections and diarrhea were more common than on placebo ¹. Pancreatitis, raised pancreatic enzymes and morphea have also been reported ¹.

Does zilucoplan work for ALS?

No. In the HEALEY ALS Platform Trial it did not slow ALS progression and was stopped early for futility ¹⁰.

Is zilucoplan banned in sport?

It is not named on the 2026 WADA Prohibited List ¹³.

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Sources

Curious how a compound like this one becomes an approved medicine? The Academy track How a peptide becomes a medicine walks through it. You can try the Academy free first.

Last reviewed 2026-10-30 · How we research · Found an error? See our corrections policy.