- Biologic License Application (BLA) designated Priority Review by FDA and seeks approval for rozanolixizumab for the treatment of adults with generalised 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 Authorisation 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
UCB, a global biopharmaceutical company, announced on 6th January 2023 that the US Food and Drug Administration (FDA) has accepted the company’s filing to review a Biologic License Application (BLA) for its investigational treatment rozanolixizumab, and that the Agency has granted Priority Review.1 Rozanolixizumab is a subcutaneous (SC) monoclonal antibody targeting the neonatal Fc receptor (FcRn) for the treatment of adults with generalised myasthenia gravis (gMG) who are anti-acetycholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive2.
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 applications3. Priority Review designation means the FDA’s goal is to take action on an application within 6 months, compared to 10 months under standard review3. In 2019, the US FDA granted orphan drug designation to rozanolixizumab for the treatment of MG.4
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 European Medicines Agency (EMA) validation of the Marketing Authorisation Application (MAA) for rozanolixizumab for the treatment of adults with AChR or MuSK antibody positive gMG who require treatment in addition to steroids or non-steroidal immunosuppressants. Validation confirms that the application is complete and the formal review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP) can begin. Orphan designation was granted by the European Commission in April 2020 to rozanolixizumab for the treatment of myasthenia gravis.5
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. The FDA’s decision to assess rozanolixizumab via their priority review process, as well as the recent filing of the MAA in Europe, brings us important steps further on our journey towards approvals for rozanolixizumab. We look forward to working with the FDA and EMA to help bring this new treatment option to patients.Charl van Zyl, Executive Vice President Neurology Solutions & Head of EU/International Markets, UCB
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 U.S. the prevalence of MG is estimated at 14 to 20 per 100,000 population; approximately 36,000 to 60,000 cases.4 In Europe, the prevalence is estimated at 10 per 100,000 population.8
Data from the MycarinG study
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 Iris Loew-Friedrich, Executive Vice-President and Chief Medical Officer at UCB. “Through rozanolixizumab and zilucoplan, we intend to bring two medicines with different mechanisms of action that have the potential to provide targeted treatment options to patients. With our gMG pipeline, we hope to address both drivers of disease pathology and which account for approximately 95% of people living with gMG. Priority Review Designation by the FDA for rozanolixizumab reflects the extent to which our science speaks for itself in potentially addressing the significant unmet needs still faced by the gMG community.”
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 U.S. FDA for the treatment of adults with AChR antibody positive gMG. Additionally, zilucoplan received MAA validation from the EMA for the treatment of adults with AChR antibody positive gMG and who require treatment in addition to steroids or non-steroidal immunosuppressants.10,11,12
- Data on file.
- 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.
- US Food and Drug Administration, https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review, Accessed January 2023
- US Food and Drug Administration https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=669918 Accessed January 2023
- European Medicines Agency, EU/3/20/2272: Orphan designation for the treatment of myasthenia gravis https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3202272 Accessed January 2023
- Myasthenia Gravis Foundation of America. Clinical Overview of MG. https://myasthenia.org/Professionals/Clinical-Overview-of-MG. Accessed January 2023
- Hansen JS, et al. Mortality in myasthenia gravis: A nationwide population-based follow-up study in Denmark. Muscle Nerve. 2016;53:73-77.
- 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 January 2023.
- Bril V, et al. Rozanolixizumab in generalized myasthenia gravis: Responder analyses from the Phase 3 MycarinG study. Poster 204, AANEM 2022.
- 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)
- US Food and Drug Administration https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=699319. Accessed January 2023
- Data on file.
- Chen J, et al. Incidence, mortality, and economic burden of myasthenia gravis in China: A nationwide population-based study. Lancet Reg Health West Pac: 2020;5:100063.
- National institute of Neurological Disorders and Stroke. 2022. Myasthenia Gravis Fact Sheet. https://www.ninds.nih.gov/myasthenia-gravis-fact-sheet. Accessed January 2023.
- 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
- Myasthenia Gravis Foundation of America. MG Quick Facts. https://myasthenia.org/MG-Education/MG-Quick-Facts Accessed January 2023
- ClinicalTrials.gov ‘A Study to Test Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis’: https://clinicaltrials.gov/ct2/show/NCT03971422. Accessed January 2023.
- 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).