UCB announces rozanolixizumab BLA for the treatment of generalized myasthenia gravis filed with U.S. FDA and designated for Priority Review
- Biologic License Application (BLA) designated Priority Review by FDA and seeks approval for rozanolixizumab for the treatment of adults with generalized myasthenia gravis (gMG) who are anti-acetycholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive
- Rozanolixizumab FDA Priority Review follows recent
European Medicines Agency(EMA) validation of the Marketing Authorization Application (MAA) for rozanolixizumab in adults with gMG
- FDA and EMA submissions based on pivotal Phase 3 MycarinG study in gMG which demonstrated treatment with rozanolixizumab resulted in clinically meaningful and statistically significant improvements in MG specific outcomes
- UCB expects to receive feedback from the agencies in Q2 of 2023
BRUSSELS and ATLANTA,
A FDA Priority Review designation is typically granted by the Agency to a medicine which, if approved, could deliver significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.3 Priority Review designation means the
The safety and efficacy of rozanolixizumab have not been established and they are not currently approved for use in any indication by any regulatory authority worldwide.
The FDA Priority Review designation follows the recent
UCB expects to receive feedback from both the FDA and EMA during the second quarter of 2023.
"People living with MG suffer from unpredictable, fluctuating, and debilitating symptoms that have a huge impact on their lives, and there is a clear need for additional targeted treatments. We are firmly committed to supporting the gMG community by providing solutions to help improve outcomes for patients and reduce the day-to-day burden of the disease," said
gMG is a chronic and unpredictable auto-immune disease in which pathogenic autoantibodies can impair synaptic transmission at the neuromuscular junction by targeting specific proteins on the post-synaptic membrane. This disrupts the ability of the nerves to stimulate the muscle and results in a weaker contraction.6 People living with gMG can experience a variety of symptoms, including drooping eyelids, double vision, and difficulty in swallowing, chewing and talking, as well as severe muscle weakness that can result in life-threatening weakness of the muscles of respiration.4,7 In the
The Priority Review BLA and the MAA are based on data from the pivotal Phase 3 MycarinG study (NCT03971422), in which rozanolixizumab demonstrated statistically significant and clinically meaningful improvements in MG-specific outcomes in patients with AChR MuSK antibody positive MG. In the primary endpoint, rozanolixizumab significantly reduced MG-ADL from baseline to Day 43. Rozanolixizumab showed an LS mean difference vs placebo (95% CI) of -2.59 points at the 7mg/kg dose and -2.62 points at the 10mg/kg dose.9
Furthermore, a greater percentage of patients in the rozanolixizumab 7mg/kg and 10mg/kg arms than the placebo arm achieved a 2.0-point or greater improvement (p<0.001) in MG-ADL, a 3.0-point or greater improvement in Quantitative Myasthenia Gravis (QMG) scores and a 3.0-point or greater improvement in Myasthenia Gravis Composite (MGC) scores7, demonstrating clinically meaningful reductions in these assessments.
Rozanolixizumab demonstrated an acceptable safety and tolerability profile with similar occurrences of TEAEs between both doses. A higher proportion of TEAEs occurred in the active treatment arms versus placebo (81.3% for 7 mg/kg, 82.6% for 10 mg/kg and 67.2% for placebo) and were comparable between the rozanolixizumab groups. The most frequently reported TEAEs were headache, diarrhea, pyrexia, and nausea. A higher incidence of headache was reported in the rozanolixizumab groups versus placebo, with most cases mild to moderate and severe cases generally managed with non-opioid analgesics. Treatment discontinuation rates due to TEAEs were low.7
In the MycarinG study, 200 patients were randomised 1:1:1 to receive weekly rozanolixizumab 7 mg/kg (N=66), 10 mg/kg (N=67) or placebo (N=67) for 6 weeks, which was followed by an 8-week observation period.6
Patients living with MG may experience high disease and treatment burden resulting in a significant impact on their daily lives
If approved, rozanolixizumab has the potential to address unmet needs of gMG patients," said
UCB is currently investigating two potential therapies with different modes of action for the treatment of gMG. Alongside rozanolixizumab, a NDA for zilucoplan – a subcutaneous self-administered peptide inhibitor of complement component 5 (C5 inhibitor) has recently been filed with the
For further information, contact UCB:
Corporate Communications, Media Relations
Myasthenia gravis is a rare disease impacting more than 700,000 people worldwide.13 People living with gMG can experience a variety of symptoms, including drooping eyelids, double vision, difficulty swallowing, chewing and talking, as well as severe muscular weakness that can result in life threatening weakness of the muscles of respiration.4
gMG is a chronic and unpredictable auto-immune disease in which pathogenic autoantibodies can impair synaptic transmission at the neuromuscular junction (NMJ) by targeting specific proteins on the post-synaptic membrane. This disrupts the ability of the nerves to stimulate the muscle and results in a weaker contraction.4,14 gMG can occur in any race, although previous studies have shown that women are more often impacted than men.15,16 Most patients with gMG have pathogenic IgG antibodies that disrupt the transmission of nerve impulses to muscles in the NMJ and some activate the complement cascade.1 Complement-mediated destruction via MAC formation is a key mechanism causing damage at the NMJ and is the key driver of disease in AChR antibody positive gMG gMG.
The MycarinG study (NCT03971422) is a multi-center, Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of rozanolixizumab in adult patients with gMG, with an open-label extension. The primary endpoint for the MycarinG study is change from baseline to day 43 in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score, an eight-item patient-reported scale developed to assess MG symptoms and their effects on daily activities. Additional endpoints include response rates, changes in the Myasthenia Gravis composite (MGC) score, the Quantitative MG (QMG) score, patient-reported outcomes and adverse events (AEs). The majority of patients taking part in the MycarinG study opted to enroll in the open label extensions to this clinical trial. As a result, UCB is exploring the potential for further extension studies into this treatment.
For more information about the trial, visit https://clinicaltrials.gov/ct2/show/NCT03971422.
Rozanolixizumab is a SC administered, humanized monoclonal antibody that specifically binds, with high affinity, to human neonatal Fc receptor (FcRn). It has been designed to block the interaction of FcRn and Immunoglobulin G (IgG), accelerating the catabolism of antibodies and reducing the concentration of pathogenic IgG autoantibodies.1,18
Rozanolixizumab is under clinical development with the aim of improving the lives of people with pathogenic IgG-autoantibody-driven autoimmune diseases. In 2019, the
The safety and efficacy of rozanolixizumab have not been established and it is not approved for use in any indication by any regulatory authority worldwide.
Zilucoplan is a once-daily SC, self-administered peptide inhibitor of complement component 5 (C5 inhibitor) under clinical development by UCB in gMG. As a C5 inhibitor, zilucoplan inhibits complement-mediated damage to the neuromuscular junction through its targeted dual mechanism of action.8 In 2019, the
The safety and efficacy of zilucoplan have not been established and it is not currently approved for use in any indication by any regulatory authority worldwide.
At UCB, we don't just see patients or population sizes, we see people in need. Through decades of serving the neurology and immunology communities, we have improved lives with impactful medicines and by enhancing the social and emotional well-being of patients. As a continuation of our heritage, we are now expanding our efforts to tackle rare neurological and immunological diseases where current options offer little hope, including investigational treatments for gMG, myelin oligodendrocyte glycoprotein antibody-associated disease (MOG-AD) and autoimmune encephalitis (AIE).
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1 Data on file.
2 Smith B, et al. Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration. MAbs. 2018;10:1111-30.
7 Hansen JS, et al. Mortality in myasthenia gravis: A nationwide population-based follow-up study in
8 Salari N, et al. Global prevalence of myasthenia gravis and the effectiveness of common drugs in its treatment: a systematic review and meta-analysis. J Transl Med 19, 516 (2021). https://doi.org/10.1186/s12967-021-03185-7. Accessed
9 Bril V, et al. Rozanolixizumab in generalized myasthenia gravis: Responder analyses from the Phase 3 MycarinG study. Poster 204, AANEM 2022.
10 Howard J, 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 2022 1;77(5)
12 Data on file.
13 Chen J, et al. Incidence, mortality, and economic burden of myasthenia gravis in
14 National institute of Neurological Disorders and Stroke. 2022. Myasthenia Gravis Fact Sheet. https://www.ninds.nih.gov/myasthenia-gravis-fact-sheet. Accessed
15 Dong D, et al. Gender differences in quality of life among patients with myasthenia gravis in China. Health and Quality of Life Outcomes 2020 18;296
17ClinicalTrials.gov 'A Study to Test Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis': https://clinicaltrials.gov/ct2/show/NCT03971422. Accessed
18 Kiessling P, et al. The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: A randomized phase 1 study. Sci Transl Med. 2017;9(414:eaan1208).
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