• 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, January 6, 2023 – 7:00 AM ET  – UCB, a global biopharmaceutical company, today announced that the U.S. 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.¹Rozanolixizumab is a subcutaneous (SC) monoclonal antibody targeting the neonatal Fc receptor (FcRn) 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.²

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 FDA’s goal is to take action on an application within 6 months, compared to 10 months under standard review.³ In 2019, the U.S. 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 Authorization 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,” said Charl van Zyl,  Executive Vice President Neurology Solutions & Head of EU/International Markets, UCB. “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.”

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

For further information, contact UCB: 

Brand Communications, Rare Diseases
Jim Baxter
T+32.2.473.78.85.01 
jim.baxter@ucb.com 

U.S. Communications, Rare Diseases
Daphne Teo
T +1.770.880.7655
daphne.teo@ucb.com

Corporate Communications, Media Relations
Laurent Schots 
T+32.2.559.92.64  
Laurent.schots@ucb.com 

Investor Relations
Antje Witte         
T +32.2.559.94.14 
antje.witte@ucb.com

About Generalized Myasthenia Gravis (gMG)

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.

About the rozanolixizumab MycarinG study¹⁷

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.

About rozanolixizumab

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 US FDA granted orphan drug designation to rozanolixizumab for the treatment of myasthenia gravis.² Orphan designation was granted in 2020 by the European Commission for rozanolixizumab to the treatment of myasthenia gravis.³

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.

About zilucoplan

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 US FDA granted orphan drug designation to zilucoplan for the treatment of myasthenia gravis.⁹ Orphan designation was granted in 2022 by the European Commission to zilucoplan for the treatment of myasthenia gravis.¹⁰

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.

About UCB in Rare Diseases 

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).

About UCB 

UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With approximately 8,600 people in approximately 40 countries, the company generated revenue of €5.8 billion in 2021. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news.

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Given these uncertainties, you should not place undue reliance on any of such forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labelling in any market, or at any particular time, nor can there be any guarantee that such products will be or will continue to be commercially successful in the future.

UCB is providing this information, including forward-looking statements, only as of the date of this press release and it does not reflect any potential impact from the evolving COVID-19 pandemic, unless indicated otherwise. UCB is following the worldwide developments diligently to assess the financial significance of this pandemic to UCB. UCB expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report or reflect any change in its forward-looking statements with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless such statement is required pursuant to applicable laws and regulations. 

Additionally, information contained in this document shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any offer, solicitation or sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such jurisdiction. 

References

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.
3. US Food and Drug Administration, https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review, Accessed January 2023
4. US Food and Drug Administration
   https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=669918 Accessed January 2023
5. 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
6. Myasthenia Gravis Foundation of America. Clinical Overview of MG. https://myasthenia.org/Professionals/Clinical-Overview-of-MG. Accessed January 2023
7. Hansen JS, et al. Mortality in myasthenia gravis: A nationwide population-based follow-up study in Denmark. Muscle Nerve. 2016;53:73-77.
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 January 2023.
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)
11. US Food and Drug Administration https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=699319. Accessed January 2023
12. Data on file.
13. 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.
14. National institute of Neurological Disorders and Stroke. 2022. Myasthenia Gravis Fact Sheet. https://www.ninds.nih.gov/myasthenia-gravis-fact-sheet. Accessed January 2023.
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
16. Myasthenia Gravis Foundation of America. MG Quick Facts. https://myasthenia.org/MG-Education/MG-Quick-Facts Accessed January 2023
17. 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.
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).