Investigating a gMG Therapy, Part 2: The Secondary Endpoint Results, Including MG Symptoms PRO

Transcript

Dr. Edmundson:
Hello. I’m Dr. Edmundson. I'm a clinical neurologist and I've been treating patients with generalized myasthenia gravis, or gMG, for 7 years. I'm looking forward to sharing information with you about RYSTIGGO, a targeted therapy approved to treat adult patients with gMG.¹ 

Generalized myasthenia gravis, or gMG, is a chronic and unpredictable autoimmune disease characterized by muscle weakness and fatigue.³ The daily unpredictability of fatigue symptoms makes it a key challenge that impacts patients physically, socially, and psychologically.^4,5 A real-world study of almost 500 patients with gMG found that nearly half were affected by fatigue.² Given its prevalence, there is a need for outcome measures that focus on fatigue to evaluate severity and response to treatment.

In this video we will explore the results for the secondary endpoints in the RYSTIGGO pivotal trial and explain the Myasthenia Gravis Symptoms Patient-Reported Outcome or MG Symptoms PRO. MG Symptoms PRO is a new outcome measure used in the RYSTIGGO clinical trials that assesses physical fatigue, along with other symptoms of gMG.^3,6 MG Symptoms PRO was part of the planned efficacy analysis in the RYSTIGGO pivotal study. However, efficacy or clinical significance of the results should be interpreted with caution.

RYSTIGGO is the first and only FDA-approved targeted treatment for both anti-AChR and anti-MuSK antibody–positive adult patients with gMG.¹ The efficacy and safety of RYSTIGGO in adults with anti-AChR and anti-MuSK antibody–positive gMG were established in MycarinG, a multicenter, randomized, double-blind, placebo-controlled Phase 3 study.^1,3 Before we review the secondary endpoints in the RYSTIGGO pivotal study, let’s quickly ground ourselves in the results for the primary endpoint.

As discussed in the Pivotal Study MG-ADL results video, the primary endpoint in this study measured the change from baseline to Week 6 in Myasthenia Gravis Activities of Daily Living, or MG-ADL score. Patients taking RYSTIGGO experienced a statistically significant and clinically meaningful reduction in MG-ADL total score at Week 6 compared with patients treated with placebo. Clinically meaningful was established as a 2-point or greater improvement in MG-ADL total score.^1,3 To learn more about the primary endpoint and other MG-ADL results in MycarinG, watch the Pivotal Study MG-ADL Results video on RystiggoHCP.com. Now, let’s jump into our review of the secondary endpoint results.

Two of the key secondary endpoints in the pivotal study included change from baseline to Week 6 in Quantitative Myasthenia Gravis, or QMG, score, and Myasthenia Gravis Composite, or MGC, score. Both the QMG and MGC scales are widely used in gMG clinical trials, so we will not go into great detail about these outcome measures here.^1,3,7 Patients in both RYSTIGGO dose groups experienced a statistically significant and clinically meaningful improvement from baseline to Week 6 in QMG scores.^1,3 MGC scores were also statistically significant and clinically meaningful from baseline to Week 6 in both RYSTIGGO dose groups. Clinically meaningful was established as a 3-point or greater improvement in both QMG and MGC scores.^3,8 

Another key secondary endpoint was the change from baseline to Week 6 in MG Symptoms PRO scores.³ MG Symptoms PRO was part of the planned efficacy analysis; however, efficacy or clinical significance of the data should be interpreted with caution. MG Symptoms PRO is a novel outcome measure, developed by UCB and used in the RYSTIGGO clinical trials, that complements established clinical outcome measures.^3,6 

Three domains of MG Symptoms PRO were evaluated in the MycarinG pivotal study: muscle weakness fatigability, physical fatigue, and bulbar muscle weakness. This is the first myasthenia gravis outcome measure to have a stand-alone assessment of physical fatigue.^3,6,9 The muscle weakness fatigability domain evaluates use-induced reduction in the ability of proximal, ocular, bulbar, and respiratory muscles to function.⁶ The physical fatigue domain evaluates symptoms like body and limb muscle weakness, lack of energy or strength, and heaviness.⁶ And the bulbar muscle weakness domain evaluates symptoms like mouth drooping and difficulties chewing and swallowing.⁶

MG Symptoms PRO uses a modular approach by focusing on each symptom separately and includes more items than other outcome measures.⁶ The patient's symptoms are measured over a 7-day period, thereby capturing the daily fluctuations often experienced by patients with gMG.⁶ A score ranging from 0-100 is calculated for each domain, with a higher score indicating greater symptom severity.⁶ Patients in both RYSTIGGO dose groups experienced a statistically significant improvement in muscle weakness fatigability, physical fatigue, and bulbar muscle weakness scores from baseline to Week 6 in the pivotal study.^3,8 As I've already mentioned, MG Symptoms PRO was part of the planned efficacy analysis, but the efficacy or clinical significance of this data should be interpreted with caution.

As we've already reviewed in the MG-ADL results video, the most frequently reported adverse reactions were headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea.¹ Additionally, RYSTIGGO may increase the risk of infection. Delay administration of RYSTIGGO in patients with an active infection and monitor for signs and symptoms of infection in patients treated with RYSTIGGO.¹ Serious events of aseptic meningitis have been reported with RYSTIGGO. If symptoms that are consistent with aseptic meningitis develop, a diagnostic workup and treatment should be initiated according to the standard of care.¹ Angioedema and rash have occurred in patients treated with RYSTIGGO. If a hypersensitivity reaction occurs, discontinue the RYSTIGGO infusion and start appropriate therapy.¹

Thank you for joining me to review the results for the key secondary endpoints in the RYSTIGGO pivotal study and to learn more about the novel outcome measure, MG Symptoms PRO.³ Remember that this video is just one in a series of educational videos about RYSTIGGO. Visit RystiggoHCP.com to view the next video about the RYSTIGGO extension studies and to explore more about RYSTIGGO and its role in the treatment of anti-AChR and anti-MuSK antibody–positive gMG.¹

Voiceover: 
INDICATION
RYSTIGGO (rozanolixizumab-noli) is indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Infections: RYSTIGGO may increase the risk of infection. Delay RYSTIGGO administration in patients with an active infection until the infection is resolved. During treatment with RYSTIGGO, monitor for clinical signs and symptoms of infection. If serious infection occurs, administer appropriate treatment and consider withholding RYSTIGGO until the infection has resolved.

Immunization
Immunization with vaccines during RYSTIGGO treatment has not been studied. The safety of immunization with live or live-attenuated vaccines and the response to immunization with any vaccine are unknown. Because RYSTIGGO causes a reduction in IgG levels, vaccination with live-attenuated or live vaccines is not recommended during treatment with RYSTIGGO. Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with RYSTIGGO.

Aseptic Meningitis: Serious adverse reactions of aseptic meningitis (also called drug-induced aseptic meningitis) have been reported in patients treated with RYSTIGGO. If symptoms consistent with aseptic meningitis develop, diagnostic workup and treatment should be initiated according to the standard of care.

Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema and rash, were observed in patients treated with RYSTIGGO. Management of hypersensitivity reactions depends on the type and severity of the reaction. Monitor patients during treatment with RYSTIGGO and for 15 minutes after for clinical signs and symptoms of hypersensitivity reactions. If a reaction occurs, institute appropriate measures if needed.

ADVERSE REACTIONS
In a placebo-controlled study, the most common adverse reactions (reported in at least 10% of RYSTIGGO-treated patients) were headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea. Serious infections were reported in 4% of patients treated with RYSTIGGO. Three fatal cases of pneumonia were identified, caused by COVID-19 infection in two patients and an unknown pathogen in one patient. Six cases of infections led to discontinuation of RYSTIGGO.

Please see full Prescribing Information at www.RystiggoHCP.com

References:

1. RYSTIGGO [Prescribing Information]. Smyrna, GA: UCB, Inc.
2. Mahic M, Bozorg AM, DeCourcy JJ,et al. Physician-reported perspectives on myasthenia gravis in the United States: a real-world survey. Neurol Ther. 2022;11(4):1535-1551. doi:10.1007/s40120-022-00383-3
3. 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
4. Law N, Davio K, Blunck M, et al. The lived experience of myasthenia gravis: a patient-led analysis. Neurol Ther. 2021;10(2):1103-25. doi:10.1007/s40120-021-00285-w
5. Jackson K, Parthan A, Lauher-Charest M, et al. Understanding the symptom burden and impact of myasthenia gravis from the patient's perspective: a qualitative study. Neurol Ther. 2023;12(1):107-128. doi:10.1007/s40120-022-00408-x
6. 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. 2023:1-18. doi:10.1007/s40120-023-00464-x
7. Thomsen JLS, Andersen H. Outcome measures in clinical trials of patients with myasthenia gravis. Front Neurol. 2020;11:596382. doi:10.3389/fneur.2020.596382
8. Data on file. UCB Inc., Smyrna, GA.
9. Cleanthous S, Mork AC, Regnault A, et al. Development of the Myasthenia Gravis (MG) Symptoms PRO: a case study of a patient-centred outcome measure in rare disease. Orphanet J Rare Dis. 2021;16(1):457. doi:10.1186/s13023-021-02064-0 

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