Extended indication

Zilbrysq is indicated as an add-on to standard therapy for the treatment of generalised myasthenia g

Therapeutic value

Possible benefit in ease of use

Registration phase

Registered

Product

Active substance

Zilucoplan

Domain

Neurological disorders

Reason of inclusion

New medicine (specialité)

Main indication

Muscular diseases other

Extended indication

Zilbrysq is indicated as an add-on to standard therapy for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti‑acetylcholine receptor (AChR) antibody positive.

Proprietary name

ZILBRYSQ

Manufacturer

UCB

Portfolio holder

UCB

Mechanism of action

Complement inhibitor

Route of administration

Subcutaneous

Therapeutical formulation

Injection

Budgetting framework

Extramural (GVS)

Centre of expertise

LUMC / MUCM+ / AUMC (loc. AMC)/ Radboud UMC / Erasmus MC

Additional remarks
Mechanism of Action:  zilucoplan is a synthetic macrocyclic peptide inhibitor of the terminal complement protein C5, with potential anti-inflammatory and cell protective activities. Upon subcutaneous administration, complement inhibitor zilucoplan binds to a unique site in terminal complement protein C5, which blocks C5 cleavage into C5a and C5b and prevents the C5b-dependent assembly of the membrane-attack complex (MAC). Zilucoplan also inhibits the interaction between C5b and C6, thereby further blocking MAC assembly.

Registration

Registration route

Centralised (EMA)

Type of trajectory

Normal trajectory

ATMP

No

Submission date

September 2022

Expected Registration

December 2023

Orphan drug

Yes

Registration phase

Registered

Additional remarks
Positieve CHMP-opinie in september 2023. Zorginstituut Nederland beoordeelt of zilucoplan (Zilbrysq®) vergoed kan worden. Start beoordeling dossier in mei 2024. Publicatie advies is nog niet bekend.

Therapeutic value

Current treatment options

Cholinesterase inhibitors, corticosteroids, Intravenous, Immunosuppressants, Immunoglobulins, bloodplasma transfer, Rituximab, Eculizumab, (ravulizumab)

Therapeutic value

Possible benefit in ease of use

Substantiation

De fase 2 studie is afgerond. In vergelijking met placebo laat het geneesmiddel positieve resultaten zien (1). Een fase 3 studie zou verder uitsluitsel moeten geven over de therapeutische waarde van dit geneesmiddel ten opzichte van andere beschikbare geneesmiddelen (2). Op basis van de beschikbare data wordt op dit moment verwacht dat de nieuwe complementremmers ongeveer gelijk zullen presteren aan eculizumab em/of ravulizumab.

Duration of treatment

Average day / days

Frequency of administration

1 times a day

Dosage per administration

Afhankelijk lichaamsgewicht. De aanbevolen dosis komt overeen met ongeveer 0,3 mg/kg.

References
Howard JF Jr, Nowak RJ, Wolfe GI, 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;77(5):582-592. doi:10.1001/jamaneurol.2019.5125, (NCT03315130, fase 2) (1), Studie-opzet fase 3-studie (NCT04115293) (2); NCT03971422)

Howard JF Jr, Bresch S, Genge A, 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; 22: 395–406.

Expected patient volume per year

Patient volume

150 - 300

Market share is generally not included unless otherwise stated.

References
Lanet Neurol. 2022. Juvenile myasthenia gravis: a nationwide study in Norway suggested an average annual incidence of 1·6 cases per 1 million people and a prevalence of 3·6–13·8 cases per 1 million people, with more girls affected than boys (1).
Additional remarks
In Nederland zijn geschat 3.000 patiënten met myasthenia gravis (167 per miljoen), de helft hiervan gebruikt immunosuppressiva (rond de1.500) en bij 10 tot 20% hiervan wordt wegens problemen met chronische stabiliteit derdelijns medicatie overwogen waaronder complementremmers (150 tot 300) (1).

Expected cost per patient per year

References
Fabrikant
Additional remarks
Fabrikant geeft aan dat de prijs nog niet bekend is.

Potential total cost per year

There is currently nothing known about the possible total cost.

Off label use

There is currently nothing known about off label use.

Indication extension

Indication extension

No

Other information

There is currently no futher information available.