Clinical Trial Data

CLINICAL TRIAL DATA

Rapid efficacy in
action for a broad
population of
adults with gMG1,2*

Week 6:

Statistically significant

improvements vs placebo in MG-ADL total score at Week 6 (-3.4 vs -0.8; P<0.001)1

Week 1:

Improvement observed
as early as Day 8

in total MG-ADL score after initial dose of RYSTIGGO (7 mg/kg: -1.2, 10 mg/kg: -1.3, placebo: -0.4)3†
†Based on post-hoc analysis.3

The clinical study included adult patients who were AChR or MuSK autoantibody positive, and who
had MGFA Class II-IVa disease, an MG-ADL score of ≥3 (with ≥3 points from non-ocular symptoms),
serum immunoglobulin G levels ≥5.5 gL, and who were on a stable dose of MG therapy prior to screening.1

Week 6:

Statistically significant

improvements vs placebo in MG-ADL total score at Week 6 (-3.4 vs -0.8; P<0.001)1

Week 1:

Improvement observed as early as Day 8

in total MG-ADL score after initial dose of RYSTIGGO (7 mg/kg: -1.2, 10 mg/kg: -1.3, placebo: -0.4)3†
†Based on post-hoc analysis.3

The clinical study included adult patients who were AChR or MuSK autoantibody positive, and who had MGFA Class II-IVa disease, an MG-ADL score of ≥3 (with ≥3 points from non-ocular symptoms), serum immunoglobulin G levels ≥5.5 gL, and who were on a stable dose of MG therapy prior to screening.1

PRIMARY ENDPOINT: MG-ADL

RYSTIGGO demonstrated rapid, clinically meaningful, and statistically significant improvements in patients' activities of daily living in a 6-week treatment cycle1,2‡

Change from baseline to Week 6 (Day 43) in MG-ADL total score in adults who are anti-AChR Ab+ or anti-MuSK Ab+.
Change from baseline to Week 6 (Day 43) in MG-ADL total score in adults who are anti-AChR Ab+ or anti-MuSK Ab+.
Change from baseline to Week 6 (Day 43) in MG-ADL total score in adults who are anti-AChR Ab+ or anti-MuSK Ab+.

The efficacy of RYSTIGGO for the treatment of adult patients with anti-AChR Ab+ and anti-MuSK Ab+ gMG was established in an up to 18-week, multicenter, randomized, double-blind, placebo-controlled study. In the study, 200 patients were randomized 1:1:1 to receive weight-tiered doses of RYSTIGGO (n=133), either 7 mg/kg of RYSTIGGO (n=66) or 10 mg/kg of RYSTIGGO (n=67), or placebo (n=67). The study included a 4-week screening period and a 6-week treatment period followed by 8 weeks of observation.1

GO TO THE STUDY DESIGN

MG-ADL MEASURES

MG-ADL assesses the impact of gMG on daily functions of 8 symptoms on a scale of 0-3, with total scores ranging from 0-24. Higher scores are interpreted as greater impairments.1 An improvement of ≥2 points was established as clinically meaningful.2 Measures include4:

  • Voice/speech problems
  • Chewing
  • Swallowing
  • Breathing
  • Brushing teeth and/or combing hair
  • Rising from a chair
  • Diplopia
  • Eyelid droop

EXPLORATORY SECONDARY endpoint

MG-ADL Responder Rate2

MG-ADL responder (≥2.0-point improvement from baseline) at Week 6 (Day 43)2

MG-ADL >2x more responders vs placebo.
MG-ADL >2x more responders vs placebo.

Study limitations: MG-ADL Responder Rate was a prespecified secondary endpoint not controlled for multiplicity; therefore, data should be interpreted with caution and conclusions cannot be drawn.

MG-ADL SUBGROUP ANALYSIS: MuSK+

The first and only treatment indicated for adult patients with anti-MuSK Ab+ gMG1

Subgroup analysis of the primary efficacy endpoint: mean MG-ADL change from baseline to Week 6 (Day 43) in participants with anti-MuSK Ab+ gMG.5

In a subgroup analysis, study participants with anti-MuSK Ab+ gMG showed improvements in MG-ADL scores vs placebo after the 6-week treatment cycle2

Subgroup analysis of study participants with anti-Musk Ab+ gMG showed improvements in MG-ADL scores vs placebo after the 6-week treatment cycle.
Subgroup analysis of study participants with anti-Musk Ab+ gMG showed improvements in MG-ADL scores vs placebo after the 6-week treatment cycle.

Subgroup analysis: MG-ADL responder rate at Week 6 (Day 43)2

All patients with anti-MuSK Ab+ gMG who received RYSTIGGO and had data available at Week 6 (Day 43) were MG-ADL responders2

100% of patients with anti-MuSK Ab+ gMG were clinical responders to RYSTIGGO (n=12).
100% of patients with anti-MuSK Ab+ gMG were clinical responders to RYSTIGGO (n=12).

#A clinical responder was established as a patient with a ≥2-point improvement in the total MG-ADL score compared to baseline at Week 6 (Day 43). Clinical responder data were not collected for one patient in the RYSTIGGO 10 mg/kg group who discontinued treatment.2,3

Study limitations: MG-ADL Responder Rate was a prespecified secondary endpoint not controlled for multiplicity; therefore, data should be interpreted with caution and conclusions cannot be drawn.

OTHER MG-ADL EFFICACY ENDPOINT

Minimal Symptom Expression (MSE) rates observed during the pivotal study2

Proportion of patients achieving MSE during treatment and observation in the pivotal study2

Patients who reached MSE achieved an MG-ADL total score of 0 to 1 at any time up to and including Week 6 (Day 43) of the pivotal study.
Patients who reached MSE achieved an MG-ADL total score of 0 to 1 at any time up to and including Week 6 (Day 43) of the pivotal study.

MSE was an exploratory endpoint and not controlled for multiplicity. Therefore, data should be interpreted with caution and conclusions cannot be drawn.

SECONDARY ENDPOINTS

RYSTIGGO demonstrated statistically significant improvements across key secondary efficacy outcome measures vs placebo1-3

Change from baseline to Week 6 (Day 43) was measured in:

**MG Symptoms PRO was part of the planned efficacy analysis; however, efficacy or clinical significance should be interpreted with caution.

OTHER ENDPOINT

Reduction in immunoglobulin G (IgG) levels1,3

A reduction in total IgG serum concentrations was observed in both RYSTIGGO treatment groups. Decreases in AChR autoantibody and MuSK autoantibody levels followed a similar pattern.

Reduction in circulating IgG.
Reduction in circulating IgG.
Reduction in circulating IgG.

Study limitations: The pharmacological effect of RYSTIGGO was assessed by measuring the decrease in serum IgG levels; the clinical significance of this data has not been established.

EXTENSION STUDIES: POOLED DATA ANALYSIS

Improvements were observed in patients receiving subsequent cycles of RYSTIGGO3

Improvements in MG-ADL across each subsequent 6-week treatment cycle3

Improvements in MG-ADL across each subsequent 6-week treatment cycle.
Improvements in MG-ADL across each subsequent 6-week treatment cycle.

The most common adverse reactions being observed with repeated cyclic treatment were consistent with adverse reactions observed in the pivotal study1,3

||||Treatment initiation on Day 1.3
Interim analysis as of July 8, 2022.3

EXTENSION STUDY DESIGNS

Minimal Symptom Expression (MSE) rates through 6 subsequent cycles of RYSTIGGO

Exploratory endpoint: Proportion of patients achieving MSE with each subsequent cycle of RYSTIGGO3

Patients who reached MSE achieved an MG-ADL total score of 0 to 1 at any visit for each 6-week cycle and observation period without the use of rescue therapy during the extension studies
Patients who reached MSE achieved an MG-ADL total score of 0 to 1 at any visit for each 6-week cycle and observation period without the use of rescue therapy during the extension studies

¶¶Day 43.

MSE was an exploratory endpoint and not controlled for multiplicity. Therefore, data should be interpreted with caution and conclusions cannot be drawn. 

Data should be interpreted with caution given the decreasing number of patients receiving subsequent treatment cycles. 

Majority of patients had treatment-free intervals between 4 and 8 weeks3

Time to subsequent symptom-driven treatment cycle from last subcutaneous infusion3

Time to subsequent symptom-driven treatment cycle
Time to subsequent symptom-driven treatment cycle

Interim analysis as of July 8, 2022.3

  • The median time between treatment cycles was 8 weeks (56 days) for patients treated with RYSTIGGO who initiated 4 cycles1##
  • The safety of initiating subsequent cycles sooner than 9 weeks (63 days) from the start of the previous treatment cycle has not been established1

##This is equivalent to 14 weeks (98 days) from the start of the previous treatment cycle.1

Ab+=antibody positive; AChR=acetylcholine receptor; CI=confidence interval; gMG=generalized myasthenia gravis; LS=least squares; MG-ADL=Myasthenia Gravis Activities of Daily Living; MGFA=Myasthenia Gravis Foundation of America; MG Symptoms PRO/MGSPRO=Myasthenia Gravis Symptoms Patient-Reported Outcome; MuSK=muscle-specific tyrosine kinase; Nsub=number of participants with an MSE assessment; SE=standard error.

 

References:

  1. RYSTIGGO [Prescribing Information]. Smyrna, GA: UCB, Inc.
  2. Bril V, Drużdż A, Grosskreutz J, et al. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol. 2023;22(5):383-394. doi:10.1016/S1474-4422(23)00077-7
  3. Data on file. UCB Inc., Smyrna, GA.
  4. MG activities of daily living (MG-ADL) profile. Myasthenia Gravis Foundation of America. 1997. Accessed January 31, 2023. https://myasthenia.org/Portals/0/ADL.pdf
  5. Habib A, Kaminski H, Drużdż A, et al. Efficacy of rozanolixizumab in muscle specific kinase antibody-positive generalized myasthenia gravis: outcomes from the randomized, phase 3 MycarinG study. Paper presented at: AANEM 2022; September 21-24, 2022; Nashville, TN.
  6. QMG form. Myasthenia Gravis Foundation of America. 1997. Accessed January 31, 2023. https://myasthenia.org/Portals/0/QMG.pdf
  7. MG composite scale. Myasthenia Gravis Foundation of America. 2012. Accessed January 31, 2023. https://myasthenia.org/Portals/0/MG%20composite%20score.pdf
  8. Regnault A, Morel T, de la Loge C, et al. Measuring overall severity of myasthenia gravis (MG): evidence for the added value of the MG Symptoms PRO. Neurol Ther. 2023:12(5):1573-1590. doi:10.1007/s40120-023-00464-x
  9. A study to investigate the long-term safety, tolerability, and efficacy of rozanalixizumab in adult patients with generalized myasthenia gravis. ClinicalTrials.gov identifier: NCT04124965. Updated September 5, 2023. Accessed March 8, 2024. https://clinicaItriaIs.gov/ct2/shaw/NCT04124965?term=MG0004&draw=2&rank=1
  10. A study to evaluate rozanolixizumab in study participants with generalized myasthenia gravis. ClinicalTrials.gov identifier: NCT04650854. Updated February 26, 2024. Accessed March 8, 2024. https://clinicaItriaIs.gov/ct2/show/NCT04650854?term=MG0007&draw=2&rank=1

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