UCB receives CHMP positive opinion for rozanolixizumab for treatment of adults with generalized myasthenia gravis in Europe
- The Committee for Medicinal Products for Human Use (CHMP) positive opinion1 is based on the pivotal Phase 3 MycarinG study in generalized myasthenia gravis (gMG) in adult patients,2 which demonstrated treatment with rozanolixizumab resulted in statistically significant and clinically meaningful improvements in gMG-specific outcomes compared to placebo,2 including everyday activities such as breathing, talking, swallowing, and being able to rise from a chair3
- If approved by the European Commission, rozanolixizumab will be the first emerging therapy approved in Europe for adults with both anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody-positive gMG, the two most common subtypes of gMG
- The decision follows CHMP positive opinion for UCB’s zilucoplan in Europe for the treatment of adult patients with gMG earlier this year, alongside similar U.S. FDA and Japanese MHLW approvals of rozanolixizumab and zilucoplan for the treatment of gMG in adult patients4,5,6,7
- UCB is the first and only company to offer a gMG-focused portfolio, providing patients and clinicians the option of two targeted therapies for both anti-AChR and anti-MuSK antibody-positive gMG
10th November 2023; UCB announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending granting marketing authorisation for rozanolixizumab as an add-on to standard therapy 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.1
Rozanolixizumab 140 mg/ml solution for injection is a humanised IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG.2 If approved by the European Commission, rozanolixizumab will be the first emerging therapy approved in Europe for adults with both anti-AChR and anti-MuSK antibody-positive gMG, the two most common subtypes of gMG.
In September 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) also issued a positive opinion recommending granting marketing authorisation for UCB’s zilucoplan in the European Union (EU) as an add-on to standard therapy for the treatment of gMG in adult patients who are anti-AChR antibody-positive4. Zilucoplan is a once-daily subcutaneously (SC)-injected, self-administered peptide inhibitor of complement component 5 (C5 inhibitor).8
In progressing a portfolio of medicines for the treatment of gMG, with the aim of providing HCPs the option of addressing either complement activation or pathogenic antibodies for appropriate patients, UCB hopes to offer a comprehensive portfolio of targeted therapeutics, embodying a commitment to addressing the gMG community’s unmet needs.
There is a significant need to bring more targeted, well-tolerated, effective treatment options that address the pathophysiology of gMG disease. If approved by the European Commission, UCB will be the first and only company to offer a gMG-focused portfolio with rozanolixizumab and zilucoplan, providing patients and clinicians the option of two targeted therapies. We believe that the inclusion of both anti-muscle-specific tyrosine kinase (MuSK) antibody positive patients and anti-AChR positive patients within the CHMP marketing authorization recommendation for rozanolixizumab could support clinicians to tailor their prescribing decisions to meet individual needs of their patients. This latest European gMG regulatory milestone, alongside approvals for both zilucoplan and rozanolixizumab in the U.S. and Japan in recent months, further reinforces the commitment we have made to the gMG community to help transform their experiences, outcomes and expectations. We are truly proud and excited for the future.”
IIris Loew-Friedrich, Executive Vice-President and Chief Medical Officer at UCB
The CHMP opinion for rozanolixizumab is supported by safety and efficacy data from the pivotal Phase 3 MycarinG study (NCT03971422), published in The Lancet Neurology in May 2023.2 The primary efficacy endpoint was the comparison of the change from baseline between treatment groups (rozanolixizumab 7mg/kg, rozanolixizumab 10mg/kg) or placebo in the MG-ADL score at Day 43. MG-ADL is a measurement tool that assesses the impact of gMG on daily functions of 8 items that are typically affected in gMG. These include activities such as breathing, talking, swallowing, and being able to rise from a chair.3 Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. A total score ranges from 0 to 24, with the higher scores indicating more impairment. Reductions in MG-ADL score from baseline to Day 43 were greater in the rozanolixizumab 7 mg/kg group (least-squares mean change –3.37 [SE 0.49]) and in the rozanolixizumab 10 mg/kg group (–3.40 [0.49]) than with placebo (–0.78 [0.49]; for 7 mg/kg, least-squares mean difference −2.59 [95% CI −4.09 to −1.25], p<0.001; for 10 mg/kg, −2.62 [−3.99 to −1.16], p<0.001).2
Secondary efficacy endpoints included change from baseline to Day 43 in the Myasthenia Gravis Composite (MG-C) and the Quantitative Myasthenia Gravis (QMC) scores. The MG-C is a 10-item instrument that measures the symptoms and signs of MG based on physician examination and patient history. Items are related to ptosis, double vision, eye closure, talking, chewing, swallowing, breathing, neck flexion, shoulder abduction, and hip flexion. Each item is scored on an ordinal scale with four possible categories and weighted. The total score ranges from 0 to 50, with higher scores indicating more severe impairments. The MG-C is composed of items originating from other scales (i.e., QMG, MMT, MG-ADL). A statistically significant difference favoring rozanolixizumab compared to placebo was observed in the MG-C score change from baseline to Day 43 [least squares mean difference] -3.90 (95% CI (−6.63 to −1.25), p<0.001 for rozanolixizumab 7mg/kg; least-squares mean difference −5.53 (95% CI −8.30 to −2.97), p<0.001 for rozanolixizumab 10mg/kg.2
The QMG is a 13-item categorical grading system that assesses muscle weakness. Each item is assessed on a 4-point scale where a score of 0 represents no weakness and a score of 3 represents severe weakness. A total possible score ranges from 0 to 39, where higher scores indicate more severe impairment.9 A statistically significant difference favoring rozanolixizumab compared to placebo was observed in the QMG total score change from baseline to Day 43 [least squares mean difference -3.48 (95% CI (−5.61 to −1.58), p<0.001 for rozanolixizumab 7mg/kg; least-squares mean difference −4.76 (95% CI −6.82 to −2.86), p<0.001 for rozanolixizumab 10mg/kg.2
The most common adverse reactions (reported in at least 10% of patients treated with rozanolixizumab) were headache, diarrhea and pyrexia.1
gMG is a rare, chronic, heterogeneous, unpredictable autoimmune disease characterised by dysfunction and damage at the neuromuscular junction (NMJ).10,11,12 gMG has a global prevalence of 100–350 cases per every 1 million people.11
“With the news of the CHMP’s positive opinion of rozanolixizumab, we are very proud and excited to potentially provide the gMG community with further treatment options and new hope. Following recent approvals in the U.S. and Japan, it is our commitment to bring widespread access of innovative treatment options to a broader patient population living with myasthenia gravis. And, with our two different medicines for gMG, each with a distinct mechanism of action, UCB offers the community a unique portfolio of treatments that embodies our commitment to addressing the gMG community’s unmet needs.” said Jean-Christophe Tellier, CEO, UCB. “We would like to take this time to extend our gratitude to the patients, care partners and investigators who participated in the MycarinG study, and to our employees and collaborators for their dedication and support to the gMG community.”
This announcement follows approval of rozanolixizumab and zilucoplan by the Japanese Ministry of Health, Labour and Welfare (MHLW) for treatment of gMG in adult patients (only for patients who inadequately respond to steroids or other immunosuppressants), and approval of rozanolixizumab by the U.S. Food and Drug Administration (FDA) for the treatment of gMG in adult patients who are anti-AChR or anti-MuSK antibody positive.7,5 Orphan designation was granted by the European Commission in 2020 to rozanolixizumab for the treatment of myasthenia gravis and successfully maintained after having received the positive CHMP Opinion.13
The CHMP’s positive opinion for rozanolixizumab is now being reviewed by the European Commission, which grants centralised marketing authorisations for medicinal products in the EU. Feedback from the European Commission is anticipated during Q1 2024.
- EMA CHMP Confirmation. Data on file, UCB November 2023.
- Bril V. Efficacy and safety of rozanolixizumab in patients with generalised myasthenia gravis: a randomised, double-blind, placebo-controlled, adaptive Phase 3 study MycarinG study. Lancet Neurol. 2023;22(5):383-94
- Wolfe Gl, et al. Myasthenia gravis activities of daily living profile. Neurology. 1992;52(7):1487-9
- CHMP Positive Opinion: Zilbrysq https://www.ema.europa.eu/en/medicines/human/summaries-opinion/zilbrysq. Date accessed November 2023
- RYSTIGGO® U.S. Prescribing Information
- ZILBRYSQ® U.S. Prescribing Information.
- Data on file: Japan MHLW, 25 September 2023.
- Howard JF Jr, 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(5):395-406.
- Regnault A, et al. Measuring Overall Severity of Myasthenia Gravis (MG): Evidence for the Added Value of the MG Symptoms PRO. Neurol Ther. 2023; 12:1573–1590.
- National Institute of Neurological Disorders and Stroke. 2022. Myasthenia Gravis Fact Sheet. https://www.ninds.nih.gov/health-information/disorders/myasthenia-gravis?search-term=myasthenia%20gravis%20fact%20sheet. Date accessed November 2023
- Punga AR, et al. Epidemiology, diagnostics, and biomarkers of autoimmune neuromuscular junction disorders. Lancet Neurol. 2022;21(2):176-88.
- Howard JF. Myasthenia gravis: The role of complement at the neuromuscular junction. Ann N Y Acad Sci. 2018;1412:113-128.
- European Medicines Agency. 2020. EU/3/20/2272: Orphan designation for the treatment of myasthenia gravis. https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3202272. Date accessed November 2023
- US Food and Drug Administration. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=699319. Date accessed November 2023.
- Myasthenia Gravis Foundation of America. MG Quick Facts. https://myasthenia.org/MG-Education/MG-Quick-Facts. Date accessed November 2023
- Juel VC, Massey JM. Myasthenia gravis. Orphanet J Rare Dis. 2007;2:44.