Extended indication

Generalized Myasthenia Gravis (in adult patients who are anti-acetylcholine receptor (AChR) antibo

Therapeutic value

Possible equal value

Registration phase

Registration application pending

Product

Active substance

Zilucoplan

Domain

Neurological disorders

Reason of inclusion

New medicine (specialité)

Main indication

Muscular diseases other

Extended indication

Generalized Myasthenia Gravis (in adult patients who are anti-acetylcholine receptor (AChR) antibody positive and require treatment in addition to steroids or non-steroidal immunosuppressants)

Manufacturer

UCB

Portfolio holder

UCB

Route of administration

Subcutaneous

Therapeutical formulation

Injection

Budgetting framework

Extramural (GVS)

Centre of expertise

LUMC / MUCM+ / AUMC (loc. AMC)

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

November 2023

Orphan drug

Yes

Registration phase

Registration application pending

Therapeutic value

Current treatment options

Cholinesterase inhibitors, corticosteroids, Immunosuppressants, Intravenous, Immunoglobulins, bloodplasma transfer, Rituximab, Eculizumab

Therapeutic value

Possible equal value

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.

Frequency of administration

1 times a day

Dosage per administration

tbd

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)

Expected patient volume per year

Patient volume

< 240

Market share is generally not included unless otherwise stated.

References
1) Spierziekten Nederland; Meriggioli M; Front Neurol Neurosci. 2009;26:94-108. doi: 10.1159/000212371; 3) Expert opinie
Additional remarks
In Nederland wordt de prevalentie van gegeneraliseerde Myasthenia Gravis (gMG) patiënten geschat op 1 op 10.000 inwoners. Dit komt overeen met 1.750 patiënten uitgaande van 17,5 miljoen inwoners (1). Van de gMG patiënten heeft 85% anti- acetylcholine receptor antilichamen wat neerkomt op 1.488 patiënten (2). Op basis van gebruikersaantallen is de inschatting dat er waarschijnlijk 240 patiënten in aanmerking komen (3). Er rekening mee houdend dat een deel van de patiënten kortdurend met IVIG of plasmaferse behandeld wordt in een acute crisis en niet als onderhoudsbehandeling. Dit is echter nog niet zeker .

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

There is currently nothing known about indication extensions.

Other information

There is currently no futher information available.