CLINICAL TRIAL DATA

ZILBRYSQ delivered statistically significant and sustained improvements in activities of daily living for adults with anti-AChR Ab+ gMG^1,2

Rapid and statistically significant improvements at Week 12^1,3

In the pivotal Phase 3 RAISE trial, ZILBRYSQ delivered a >4-point improvement in the ability to manage activities of daily living at Week 12 for adults with anti-acetylcholine receptor (AChR) antibody positive (Ab+) generalized myasthenia gravis (gMG).

Primary endpoint: Change from baseline (CFB) at Week 12 in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score

Primary endpoint: Mean change from baseline to Week 12 in MG-ADL total score.

The most common adverse reactions (reported in at least 10% of patients treated with ZILBRYSQ) were injection site reactions, upper respiratory tract infections, and diarrhea.¹

Clinically meaningful was defined as a ≥2-point change in MG-ADL score.³

The safety and efficacy of ZILBRYSQ were evaluated in a 12-week, multicenter, randomized, double-blind, placebo-controlled study. Patient population included patients with diagnosis of mild to severe gMG (MGFA class II-IV).¹

See study design

"This kind of potential for meaningful improvement in only 3 months is very appealing to me when I am considering ZILBRYSQ for my patients.”

Watch Dr Weiss present the RAISE Clinical Trial

MG-ADL scale overview

Myasthenia gravis activities of daily living (MG-ADL)

The MG-ADL assesses the impact of gMG on daily functions of 8 symptoms on a scale of 0-3, with total scores ranging from 0 to 24. Higher scores are interpreted as greater impairments.¹ An improvement of ≥2 points was established as clinically meaningful.³

Measures include⁴:

Talking
Chewing
Swallowing

Breathing
Brushing teeth and/or combing hair
Rising from a chair

Diplopia
Eyelid droop

Sustained efficacy through Week E84^2,5

The primary endpoint of RAISE-XT evaluated the long-term safety and tolerability of ZILBRYSQ. Please see the results here.

Sustained improvement in both arms at Week E48.

Sustained improvement in both arms at Week E84.

RAISE-XT evaluated 200 patients from either Phase 2 or 3, including 17 patients from Phase 2 who started with or switched to 0.1 mg/kg. The graphic above shows only the 183 patients continuing or switching to ZILBRYSQ at the approved dosage (0.3 mg/kg) and are solely represented in the subsequent analyses on efficacy.^2,5

*Includes pooled data of patients from Week E12-Week E84.²

MG-ADL responder rates for ZILBRYSQ in RAISE and RAISE-XT^1,2

A high proportion of patients taking ZILBRYSQ were MG-ADL clinical responders (≥ 3-point improvement from baseline) at Week 12 and Week E84.^1,2

RAISE Week 12 73% of patients were MG-ADL responders. RAISE-XT: Week E12 83% of patients were MG-ADL responders. RAISE-XT: Week E48 88% of patients were MG-ADL responders.

RAISE Week 12 73% of patients were MG-ADL responders. RAISE-XT: Week E12 85% of patients were MG-ADL responders. RAISE-XT: Week E48 87% of patients were MG-ADL responders.

MG-ADL responder rates in RAISE was an other secondary efficacy endpoint and an exploratory endpoint in RAISE-XT. Results should be interpreted with caution.^3,5

Includes pooled data of patients from Phases 2 and 3 of the clinical study who either continued on ZILBRYSQ or switched to ZILBRYSQ from placebo.²

ZILBRYSQ showed continued minimal symptom expression (MSE) in patients through Week E84²

Patients who achieved MSE in either RAISE or RAISE-XT achieved an MG-ADL score of 0 or 1 without rescue therapy.⁵

Patients taking ZILBRYSQ who achieved MSE (mITT population)

MSE was deﬁned as an MG-ADL total score of 0-1. MSE was speciﬁed as an other secondary efficacy endpoint in the RAISE study and an exploratory endpoint in RAISE-XT. Results should be interpreted with caution.^3,5

Includes pooled data of patients from Week E12-Week E84.²

100% of patients who completed the RAISE study opted into RAISE-XT.⁵

RAISE: consistent and significant improvements across key clinician- and patient-reported secondary outcome measures^1,3

Change from baseline at Week 12 in the following endpoints:

Qualitative MG (QMG) score

Statistically significant improvement in muscle strength^1,3

Secondary endpoint: CFB in QMG score at Week 12

Clinically meaningful was defined as a ≥3-point change in QMG score.³

MG Composite (MGC) score

Statistically significant improvement in gMG signs and symptoms³

Secondary endpoint: CFB in MGC score at Week 12

Clinically meaningful was defined as a 3-point change in MGC score.³

MG-Quality of Life 15-item Scale revised (MG-QoL 15r) score

Statistically significant improvements in quality of life³

Secondary endpoint: CFB in MG-QoL 15r score at Week 12

MG-Quality of Life 15-item Scale revised (MG-QoL 15r) score at Week 12.

Study Limitation: At the time of the study, no threshold for clinical meaningfulness for the MG-QoL 15r assessment had been established.³

RAISE other endpoint: complement inhibition

Patients taking ZILBRYSQ achieved complement inhibition of 97.5% by the end of Week 1^1,3

Complement activity as shown by sRBC lysis assay

The safety and efficacy of ZILBRYSQ were evaluated in a 12-week, multicenter, randomized, double-blind, placebo-controlled study. The patient population included patients with a diagnosis of mild to severe gMG (MGFA class II-IV).¹

Assessment of complement activity using sRBC lysis assay was a pharmacodynamics outcome.³

gMG=generalized myasthenia gravis; MGFA=Myasthenia Gravis Foundation of America; SD=standard deviation; sRBC=sheep red blood cell.

Secondary endpoint measures overview

Secondary endpoint measures

Quantitative Myasthenia Gravis (QMG)

QMG is a physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. Measures are assessed on a scale of 0-3, with total scores ranging from 0 to 39.¹ An improvement of ≥3 points was established as clinically meaningful.³ Measures include⁷:

Ptosis
Facial muscle weakness
Dysarthria
Grip strength
Neck flexion endurance

Diplopia
Difficulty swallowing 4 oz of water
Percentage predicted forced vital capacity
Arm and leg endurance

Myasthenia Gravis Composite (MGC)

MGC is a 10-item patient and physician assessment of the signs and symptoms of myasthenia gravis based on exam and patient history, with total scores ranging from 0 to 50. Higher scores are interpreted as greater impairments.⁸ An improvement of ≥3 points was established as clinically meaningful.³ Measures include⁸:

Ptosis
Eye closure
Chewing
Breathing
Shoulder abduction

Diplopia
Talking
Swallowing
Neck flexion/extension
Hip flexion

Myasthenia Gravis Quality of Life 15-item revised (MG-QoL 15r) scale

MG-QoL 15r is a 15-item questionnaire that allows clinicians to estimate a patient’s quality of life relevant to MG. Items on the MG-QoL 15r relate to physical, social, and psychological components and are scored from 0 (not at all) to 2 (very much). The cumulative scores range from 0 to 30, with higher scores representing worse quality of life.⁹ No threshold for clinical meaningfulness for the MG-QoL 15r change had been established.³ Measures include⁹:

Frustration
Trouble eating
Limitations at work
Hobby and activity enjoyment

Depression
Mobility
Personal grooming
Loss of independence

EXPLORE NEXT:

View study design ZILBRYSQ REMS

References:

ZILBRYSQ [Prescribing Information]. Smyrna, GA: UCB, Inc.
Leite MI, Bresch S, Hewamadduma C, et al; on behalf of the RAISE-XT study team. Long-term zilucoplan in generalised myasthenia gravis: 96-week follow-up interim analysis of RAISE-XT. Presented at European Academy of Neurology 2024 Annual Meeting; April 13-18, 2024; Helsinki, Finland. Presentation EPR-254.
Howard JF Jr, Bresch S, Genge A, et al; RAISE Study Team. 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(5):395-406. doi:10.1016/S1474-4422(23)00080-7
MG Activities of Daily Living (MG-ADL) scale. Conquer MG. September 29, 2022. Accessed November 9, 2023. https://www.myastheniagravis.org/mgactivities-of-daily-living-mg-adl-scale/
Howard JF Jr, Bresch S, Farmakidis C, 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;17(3):1–16. doi:10.1177/17562864241243186
Vu T, Genge A, Hussain Y, et al; on behalf of the RAISE investigators. Efficacy and safety of zilucoplan in myasthenia gravis: responder analysis from the randomized Phase 3 RAISE trial: poster 200. Poster presented at: American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting; September 21-24, 2022; Nashville, TN.
QMG form. Myasthenia Gravis Foundation of America. 1997. Accessed November 9, 2023. https://myasthenia.org/Portals/0/QMG.pdf
Sadjadi R, Conaway M, Cutter G, et al; MG Composite MG-QOL15 Study Group. Psychometric evaluation of the myasthenia gravis composite using Rasch analysis. Muscle Nerve. 2012;45(6):820-825.
MG-QOL15R scale. Myasthenia Gravis Rare Disease Network. 2022. Accessed November 9, 2023. https://mgnet.rarediseasesnetwork.org/sites/default/files/2023-04/mg-quality-life-15-revised.pdf