UCB (Euronext Brussels: UCB), a global biopharmaceutical company, today announced that ZILBRYSQ® (zilucoplan) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody-positive.
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[17-October-2023] |
ATLANTA, Oct. 17, 2023 /PRNewswire/ -- UCB (Euronext Brussels: UCB), a global biopharmaceutical company, today announced that ZILBRYSQ® (zilucoplan) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody-positive.1 ZILBRYSQ is the first once-daily subcutaneous, targeted peptide inhibitor of complement component 5 (C5 inhibitor)2. It is the only once-daily gMG target therapy for self-administration by adult patients with anti-AChR antibody-positive gMG. As a complement C5 inhibitor, ZILBRYSQ inhibits complement-mediated damage to the neuromuscular junction through its targeted mechanism of action.2 Benefits of self-administered treatment compared with intravenously administered treatments can include reduced travel time to and from hospitals, decreased interference with work obligations, and increased independence. Unlike monoclonal antibody C5 inhibitors, as a peptide, ZILBRYSQ can be used concomitantly with intravenous immunoglobulin and plasma exchange, without the need for supplemental dosing.2 The FDA approval of ZILBRYSQ1 is supported by safety and efficacy data from the RAISE study (NCT04115293), published in The Lancet Neurology in May 2023.2 The RAISE study was a multi-center, Phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy, safety profile, and tolerability of ZILBRYSQ in adult patients with anti-acetylcholine receptor (AChR) antibody-positive gMG. Patients were randomized in a 1:1 ratio to receive daily subcutaneous injections of 0.3 mg/kg ZILBRYSQ or placebo for 12 weeks. The study demonstrated that ZILBRYSQ delivered rapid, consistent, and statistically significant benefits in different patient-and-clinician reported outcomes at Week 12 in a broad population of adult patients with mild-to-severe anti-AChR-antibody positive gMG. The most common adverse reactions (≥10%) in patients with gMG were injection site reactions, upper respiratory tract infection, and diarrhea. “For people with gMG, the unpredictable nature of the severity and frequency of symptoms can be debilitating and can have a substantial impact on many aspects of their day-to-day lives. In addition to muscle weakness, people living with gMG experience fatigue, affecting their overall quality of life,” said James F. Howard, MD, Distinguished Professor of Neuromuscular Disease, Professor of Neurology, Medicine and Allied Health, The University of North Carolina at Chapel Hill School of Medicine and lead investigator in the RAISE trial. “ZILBRYSQ demonstrated rapid improvements in gMG symptoms at Week 12, with differences seen as early as one week, and provides a new treatment option for a broad population of AChR antibody-positive gMG patients. ZILBRYSQ is designed for continued daily use.” gMG is a rare, chronic, heterogeneous, unpredictable autoimmune disease characterized by dysfunction and damage at the neuromuscular junction (NMJ).4,5,6 Several factors are understood to be drivers of gMG disease pathology, including the complement cascade, immune cells and pathogenic Immunoglobulin G (IgG) autoantibodies. 7 In anti-AChR antibody-positive gMG, pathogenic AChR autoantibodies (IgG1 and IgG3) initiate the classical complement pathway, leading to the cleavage of C5 and the MAC (membrane attack complex) formation, damage to the NMJ, loss of AChRs and subsequent impaired synaptic transmission.6,8,9 Preventing MAC formation reduces damage to the post-synaptic membrane, reduces disruption of ionic channel conductance and helps to preserve neuromuscular transmission.8 MG has a global prevalence of 100–350 cases per every 1 million people.5 “This is an important development for the community because, with more FDA-approved treatments for generalized myasthenia gravis, physicians have additional tools to treat this disease in individualized ways that are the right fit for each individual patient,” said Samantha Masterson, President and Chief Executive Officer of the Myasthenia Gravis Foundation of America. “We are so grateful to UCB for being part of the myasthenia gravis community and their continued commitment to finding solutions for people living with this chronic, autoimmune, neuromuscular disease.” With the approval of ZILBRYSQ, alongside the company’s neonatal Fc receptor (FcRn) blocker RYSTIGGO® (rozanolixizumab-noli), which was approved earlier this year by the FDA under Priority Review designation 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, UCB’s portfolio provides healthcare professionals the option of addressing either complement activation or pathogenic auto-antibodies for appropriate patients.3,10 “With the FDA approval for ZILBRYSQ, we are very proud and excited to expand our support to the gMG community. Following the FDA approval and strong momentum with our FcRn inhibitor rozanolixizumab-noli and with our tailored patient support services and commitment to widespread access, I am confident that UCB is the only company with a portfolio of two targeted therapies with different mechanisms of action and the experience to deliver truly individualized transformational patient value to people living with this often debilitating rare disease” said Jean-Christophe Tellier, CEO, UCB. “We would like to extend our thanks to the patients, care partners, and investigators who participated in the RAISE study, and to our employees and collaborators, whose dedication and commitment to the gMG community made this important milestone possible.” The primary endpoint for the RAISE study was change from baseline to Week 12 in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score. The MG-ADL is an eight-item patient-reported outcome measure assessing MG symptoms and functional activities related to activities of daily living.11 These include activities such as breathing, talking, swallowing, and being able to rise from a chair.12 Each of the items is scored, from 0 (normal) to 3 (most severe), providing a total MG-ADL score ranging from 0 to 24, where higher scores indicate greater severity of symptoms.2 The efficacy of ZILBRYSQ was also measured, as a secondary endpoint, using the Quantitative Myasthenia Gravis (QMG) total score which 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.11 At week 12, treatment with ZILBRYSQ demonstrated a statistically significant improvement from baseline compared to placebo for MG-ADL total score and QMG total score. Other secondary endpoints included the proportion of patients with improvements of at least 3 and 5 points in the MG-ADL total score and QMG total score, respectively, at Week 12 without rescue therapy.2 “Until now, people living with gMG have only had access to C5 therapy intravenously, which can be inconvenient and time consuming. Now, with the option of ZILBRYSQ, a self-administered once-daily, subcutaneous targeted complement C5 inhibitor, we hope a broad population of mild-to-severe adult patients with AChR-antibody-positive gMG will be able to have greater independence” said Iris Loew-Friedrich, Executive Vice-President and Chief Medical Officer at UCB. “Alongside our FcRn blocker RYSTIGGO, which was approved and launched in the U.S. earlier this summer, our unique portfolio will support patients and healthcare professionals to tailor choice of treatment according to their individual needs.” \ About zilucoplan Zilucoplan is a once-daily, SC, self-administered peptide inhibitor of complement component 5 (C5 inhibitor). As the only once-daily gMG target therapy for self-administration by adult patients with anti-AChR antibody-positive gMG, zilucoplan inhibits complement-mediated damage to the neuromuscular junction through its targeted mechanism of action.2 In September 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending granting marketing authorization for zilucoplan in the European Union (EU) as an add-on to standard therapy for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti–acetylcholine receptor (AChR) antibody-positive.13 A final decision on approval in the EU is expected before the end of the year, in line with the EMA’s standard review timeline. Also in September 2023, the Japanese Ministry of Health, Labour and Welfare (MHLW) approved zilucoplan for the treatment of gMG in adult patients who inadequately respond to steroids or other immunosuppressants.14 Zilucoplan is currently under review by the Australian Therapeutic Goods Administration (TGA) and Health Canada for the treatment of adults with gMG. Responses from regulatory agencies to these submissions are expected between H2 2023 and H2 2024. Orphan designation was granted by the FDA in 2019 to zilucoplan for the treatment of myasthenia gravis.14 About generalized Myasthenia Gravis (gMG) gMG is a rare autoimmune disease with a global prevalence of 100–350 cases per every 1 million people.5 People living with gMG can experience a variety of symptoms, including severe muscular weakness that can result in double vision, drooping eyelids, difficulty with swallowing, chewing and talking, as well as life-threatening weakness of the muscles of respiration.4,16 In MG, pathogenic autoantibodies can impair synaptic transmission at the neuromuscular junction (NMJ) by targeting specific proteins on the post-synaptic membrane.17 This disrupts the ability of the nerves to stimulate the muscle and results in a weaker contraction. gMG can occur in any race, gender or age.4,16 About the RAISE study2 The primary endpoint for the RAISE study was change from baseline to Week 12 in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score. Secondary endpoints included change from baseline in the Quantitative Myasthenia Gravis (QMG) score, the Myasthenia Gravis Composite (MGC) and the Myasthenia Gravis Quality of Life 15 revised (MG-QoL15r) score from baseline to Week 12. Other secondary efficacy outcomes , time to first receipt of rescue therapy over 12 weeks, the proportion of patients with minimal symptom expression (MSE) (defined as MG-ADL of 0 or 1 without rescue therapy), the proportion of patients with a ≥3-point reduction in MG-ADL without rescue therapy and the proportion of patients with a ≥5-point reduction in QMG without rescue therapy, all measured at Week 12. Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs). Patients who completed the RAISE trial had the possibility to enter the open-label extension study, RAISE-XT (NCT04225871).2 For more information about the trial, visit https://clinicaltrials.gov/ct2/show/NCT04115293. About rozanolixizumab-noli In addition to zilucoplan, UCB’s gMG portfolio includes the FDA-approved medicine RYSTIGGO® (rozanolixizumab-noli), a subcutaneously infused monoclonal antibody targeting the neonatal Fc receptor (FcRn).9 In June 2023, rozanolixizumab-noli was approved by the FDA, for the treatment of gMG in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody-positive, having been granted Priority Review for its Biologic License Application (BLA).3,10 In September 2023, rozanolixizumab was approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for the treatment of gMG in adult patients who inadequately respond to steroids or other immunosuppressants.14 Rozanolixizumab is currently under review by the European Medicines Agency (EMA), the Australian Therapeutic Goods Administration (TGA) and Health Canada for the treatment of adults with gMG. Responses from regulatory agencies to these submissions are expected during H2 2023 and H1 2024. Important Safety Information for ZILBRYSQ® IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING What is the most important information I should know about ZILBRYSQ?
Your healthcare provider will give you a Patient Safety Card about the risk of meningococcal infection. Carry it with you at all times during treatment and for 2 months after your last ZILBRYSQ dose. Your risk of meningococcal infection may continue for several weeks after your last dose of ZILBRYSQ. It is important to show this card to any healthcare provider who treats you. This will help them diagnose and treat you quickly. ZILBRYSQ is only available through a program called the ZILBRYSQ REMS. Before you can receive ZILBRYSQ, your healthcare provider must:
ZILBRYSQ may also increase the risk of other types of serious infections.
Call your healthcare provider right away if you have new signs or symptoms of infection. Who should not use ZILBRYSQ? Do not use ZILBRYSQ if you have a Neisseria meningitidis infection. Before you use ZILBRYSQ, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What are the possible side effects of ZILBRYSQ? ZILBRYSQ may cause serious side effects, including:
The most common side effects of ZILBRYSQ include:
Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of ZILBRYSQ. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at www.fda.gov/medwatch or 1-800-FDA-1088. You may also report side effects to UCB, Inc. by calling 1-844-599-CARE [2273]. See the detailed Instructions for Use that comes with ZILBRYSQ for information on how to prepare and inject a dose of ZILBRYSQ, and how to properly throw away (dispose of) used ZILBRYSQ prefilled syringes. INDICATION
Please see the full Prescribing Information and Medication Guide for ZILBRYSQ, including Boxed Warning regarding serious meningococcal infections. Please see the Instructions for Use for the ZILBRYSQ Single-Dose Prefilled Syringe. Talk to your healthcare provider about your condition or your treatment. For more information, go to www.ZILBRYSQ.com or call 1-844-599-2273. Important Safety Information for RYSTIGGO® IMPORTANT SAFETY INFORMATION AND INDICATION WHAT IS RYSTIGGO? WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT RYSTIGGO (rozanolixizumab-noli)?
Before taking RYSTIGGO, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. WHAT ARE THE POSSIBLE SIDE EFFECTS OF RYSTIGGO?
The most common side effects of RYSTIGGO include18:
These are not all the possible side effects of RYSTIGGO. For more information, ask your healthcare provider or pharmacist. Tell your healthcare provider about any side effect that bothers you or that does not go away. Call your healthcare provider for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to UCB, Inc. by calling 1-844-599-CARE [2273]. Please see the full Prescribing Information and talk to your healthcare provider about your condition or your treatment. For further information, contact UCB: U.S. Rare Disease Communications Global Rare Disease Communications Corporate Communications, Media Relations Investor Relations 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 €5.5 billion in 2022. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news. Forward looking statements 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:
RYSTIGGO® and ZILBRYSQ® are registered trademarks of the UCB Group of Companies. View original content:https://www.prnewswire.com/news-releases/ucb-announces-us-fda-approval-of-zilbrysq-zilucoplan-for-the-treatment-of-adults-with-generalized-myasthenia-gravis-301959745.html SOURCE UCB | |||||
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