MUSK

SHANGHAI and NANJING, China and SAN JOSE, Calif., Feb. 29, 2024 /PRNewswire/ -- On February 26, 2024, the impactful international academic journal, EMBO Molecular Medicine, published the clinical data of the fully human BCMA targeting autologous CAR-T cell injection (Equecabtagene Autoleucel, Eque-cel, CT103A) for the treatment of two refractory myasthenia gravis (MG) subjects. B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis, initially demonstrated the good tolerability and safety of Eque-cel in the treatment of MG, as well as the durable clinical efficacy. MG is an autoimmune disease with acquired neuromuscular junction (NMJ) transmission disorders mediated by antibodies. Antibodies to the Acetylcholine Receptor (AChR) are the most common pathogenic antibodies; in addition, antibodies such as Muscle-Specific receptor tyrosine Kinase (MuSK), low-density Lipoprotein Receptor-related Protein 4 (LRP4), and Ryanodine Receptor (RyR), have also been found to be involved in the pathogenesis of MG. Currently, the treatment of MG is still based on cholinesterase inhibitors, glucocorticoids, immunosuppressants, intravenous immunoglobulin, plasma exchange, and thymectomy. The main causes of death in MG patients include respiratory failure and pulmonary infections. This is an investigator-initiated open-label study to evaluate the safety and efficacy of Eque-cel for the treatment of relapsed/refractory antibody-mediated idiopathic inflammatory disorders of the nervous system (NCT04561557). It was conducted by Prof. Wei Wang's team at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Two subjects with refractory MG were enrolled in this study. One was a 33-year-old female, AChR-IgG and Titin-IgG positive, who had been treated with thymectomy 21 months prior to enrollment and had not achieved clinical remission after treatment with cholinesterase inhibitors, glucocorticoids, immunosuppressants, and anti-CD20 monoclonal antibody. The other subject was a 60-year-old female, MuSK- IgG4 positive, with a 20-year history of the disease and failed the previous treatment with hormones, immunosuppressants, and anti-CD20 monoclonal antibody. The 2 subjects were treated with a single infusion of Eque-cel at the doses of 1.01×106 CAR-T/Kg and 0.96×106 CAR-T/Kg， respectively. Safety: Of the 2 subjects, only 1 subject developed grade 1 Cytokine Release Syndrome (CRS), and no Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS). All grade ≥3 hemocytopenia recovered within 4 weeks post infusion. No new safety risk was identified, and the safety profile was superior compared to that in multiple myeloma indication. Effectiveness: Clinical symptoms continued to improve over 18 months in the 2 subjects. From 3 months after the infusion, patients showed significant improvement in limb strength and vital capacity, and sustained improvement in Myasthenia Gravis-Activities of Daily Living Score (MG-ADL), Quantitative Myasthenia Gravis Score (QMG), Myasthenia Gravis-Quality of Life Score (MG-QOL), and Modified Rankin Score (mRS). No immunomodulatory therapy other than low dose pyridostigmine (90 mg/day and 60 mg/day, respectively) was used during the follow-up period. PK/PD: Eque-cel expanded well after infusion and persisted for a shorter period than that in multiple myeloma patients. Anti-AChR antibodies, anti-Titin antibodies, and anti-MuSK antibodies decreased rapidly and maintained at very low levels in both subjects after infusion. B cells and plasma cells decreased to undetectable levels in both subjects within 2 months after infusion and then recovered gradually. At 18 months post-infusion, the B cells of both subjects had returned to normal levels, with approximately 80% of them being naïve B cells, while plasma cells remained at low levels. This result suggests that the long-term efficacy of CAR-T cell therapy may be related to the reconstitution of B cells with a predominantly naïve phenotype and the continued clearance of plasma cells. The principal investigator of this study, Prof. Wei Wang of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, said "Myasthenia Gravis has a long course, is difficult to cure, and is prone to recurrence. Current treatment with traditional medications, although is able to improve symptoms of Myasthenia Gravis to a certain extent, is deficient in terms of disease control and long-term safety, and there is an urgent need for patients to have a better clinical outcome and treatment modality. In our study, it is gratifying to see that BCMA CAR-T cell therapy can prevent MG disease progression and show signs of reversal of the disease, which is expected to change the MG treatment landscape and bring hope for a cure to patients." In addition to the results of this published study, IASO Bio and a team of investigators continue to explore the safety and efficacy of Equecabtagene Autoleucel in the treatment of other antibody-mediated autoimmune diseases, including optic neuromyelitis optica spectrum disorders (NMOSD), Immune-Mediated Necrotizing Myelopathy (IMNM), and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), with an aim to change the landscape of treatment for autoimmune diseases. About IASO Bio IASO Bio is a biopharmaceutical company engaged in the discovery and development of novel cell therapies and biologics for oncology and autoimmune diseases. IASO Bio possesses comprehensive capabilities spanning the entire drug development process, from early discovery to clinical development, regulatory approval, and commercial production. The pipeline in the company includes a diversified portfolio of over 10 novel products, including Equecabtagene Autoleucel (a fully human BCMA CAR-T injection). Equecabtagene Autoleucel received New Drug Application (NDA) approval from China's National Medical Products Administration (NMPA) and U.S. FDA IND approval for the treatment of RRMM. Leveraging its strong management team, innovative product pipeline, GMP production, as well as integrated manufactural and clinical capabilities, IASO aims to deliver transformative, curable, and affordable therapies that fulfil unmet medical needs to patients in China as well as around the world. For more information, please visit or . SOURCE IASO Bio

BRUSSELS, Belgium I January 08, 2024 I UCB (Euronext Brussels: UCB), a global biopharmaceutical company, today announced that the European Commission (EC) has granted a marketing authorization for RYSTIGGO ® (rozanolixizumab) on 5th January 2024 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 humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn) resulting in the reduction of circulating IgG. 2 It is the first therapy approved in Europe for adults with anti-AChR or anti-MuSK antibody-positive gMG, the two most common subtypes of gMG. In December 2023, the EC also granted a marketing authorization for UCB’s ZILBRYSQ ® (zilucoplan) 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. “ With the European Commission approval of rozanolixizumab, alongside their recent approval of zilucoplan, I’m very excited that our gMG portfolio is now approved for use by healthcare professionals across Europe. This represents another important milestone in our ambition to deliver new and additional patient value to the gMG community and continues our launch trajectory ”, explained Jean-Christophe Tellier, CEO, UCB. “ We believe there is still a significant unmet need within the gMG community which can be addressed by bringing differentiated, generally well-tolerated, and effective treatment options to patients that address key aspects of gMG pathophysiology. We extend our gratitude to the patients, care partners, and investigators who participated in our clinical studies and who have shared their insights with us. I would also like to thank our employees and collaborators whose dedication, energy and passion have contributed to this  significant  achievement .” EC approval of 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 (approximately rozanolixizumab 7mg/kg and rozanolixizumab 10mg/kg) versus 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 approximately 7 mg/kg group (least-squares mean change –3.37 [SE 0.49]) and in the approximately 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). 1 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 approximately 7mg/kg; least-squares mean difference −5.53 (95% CI −8.30 to −2.97), p<0.001 for rozanolixizumab approximately 10mg/kg. 1 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 approximately 7mg/kg; least-squares mean difference −4.76 (95% CI −6.82 to −2.86), p<0.001 for  rozanolixizumab approximately  10mg/kg. 1 As included within the rozanolixizumab EU Summary of Product Characteristics, the most commonly reported adverse reactions were headache (48.4 %), diarrhoea (25.0 %) and pyrexia (12.5 %) 1 . gMG is a rare, chronic, heterogeneous, unpredictable autoimmune disease characterized 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 This announcement follows approvals 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), 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 , and approval of zilucoplan by the FDA for the treatment of gMG in adult patients who are AChR antibody-positive. 7,5,6 Orphan designation was granted by the European Commission in 2020 to rozanolixizumab for the treatment of myasthenia gravis and maintained after having received the positive CHMP Opinion. 13 The approval of rozanolixizumab from the EC is valid in all EU member states, as well as in the European Economic Area (EEA) countries Iceland, Liechtenstein, and Norway. UCB is committed to making rozanolixizumab available to patients as quickly as possible and anticipates European availability will commence in the first quarter of 2024. ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions . About rozanolixizumab About zilucoplan About generalized Myasthenia Gravis (gMG) gMG is a rare autoimmune disease with a global prevalence of 100–350 cases per every 1 million people. 11 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. 10,15 In gMG, pathogenic autoantibodies can impair synaptic transmission at the neuromuscular junction (NMJ) by targeting specific proteins on the post-synaptic membrane. 16 This disrupts the ability of the nerves to stimulate the skeletal muscle and results in a weaker contraction. gMG can occur in any race, gender or age. 10,15 About the MycarinG study 2 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 in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at Day 43, an eight-item patient-reported scale developed to assess MG symptoms and their effects on daily activities. Additional endpoints include changes in the Myasthenia Gravis composite (MG-C) score, the Quantitative MG (QMG) score, patient-reported outcomes at Day 43 and adverse events (AEs). The majority of patients taking part in the MycarinG study opted to enroll in the 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 . RYSTIGGO ® (rozanolixizumab) EU/EEA* Important Safety Information This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. The most commonly reported adverse reactions were headache (48.4 %), diarrhoea (25.0 %) and pyrexia (12.5 %). The adverse reactions from the placebo-controlled study in gMG are as follow : Very common (≥ 1/10) headache, diarrhoea and pyrexia; Common (≥ 1/100 to < 1/10) rash, angioedema, arthralgia and injection site reactions. Headache was the most common reaction reported in 31 (48.4 %) and 13 (19.4 %) of the patients treated with rozanolixizumab and placebo, respectively. All headaches, except 1 (1.6 %) severe headache,  were either mild (28.1 % [n=18]) or moderate (18.8 % [n=12]) and there was no increase in incidences of headache with repeated cyclic treatment. Rozanolixizumab is contra-indicated in patients with hypersensitivity to the active substance or to any of the excipients. Treatment with rozanolixizumab in patients with impending or manifest myasthenic crisis has not been studied. The sequence of therapy initiation between established therapies for MG crisis and rozanolixizumab, and their potential interactions, should be considered. Aseptic meningitis (drug induced aseptic meningitis) has been reported following rozanolixizumab treatment at a higher dose with subsequent recovery without sequelae after discontinuation. If symptoms consistent with aseptic meningitis occur, diagnostic workup and treatment should be initiated as per standard of care. Due to its mechanism of action, the use of rozanolixizumab may increase the patient’s susceptibility to infections. Treatment with rozanolixizumab should not be initiated in patients with a clinically importantactive infection until the infection is resolved or is adequately treated. During treatment with rozanolixizumab, clinical signs and symptoms of infections should be monitored. If a clinically important active infection occurs, withholding rozanolixizumab until the infection has resolved should be considered. Hypersensitivity reactions including mild to moderate rash or angioedema were observed in patients treated with rozanolixizumab. Patients should be monitored during treatment with rozanolixizumab and for 15 minutes after the administration is complete for clinical signs and symptoms of hypersensitivity reactions. If a hypersensitivity reaction occurs during administration, rozanolixizumab infusion should be discontinued and appropriate measures should be initiated if needed. Once resolved, administration may be resumed Immunisation with vaccines during rozanolixizumab therapy has not been studied. The safety of immunisation with live or live-attenuated vaccines and the response to immunisation with vaccines are unknown. All vaccines should be administered according to immunisation guidelines and at least 4 weeks before initiation of treatment. For patients that are on treatment, vaccination with live or live attenuated vaccines is not recommended. For all other vaccines, they should take place at least 2 weeks after the last infusion of a treatment cycle and 4 weeks before initiating the next cycle. Please consult the full prescribing information in relation to other side effects, full safety and prescribing information. https://www.ema.europa.eu/en . 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. References: SOURCE: UCB

The European Commission (EC) has approved UCB’s Zilbrysq (zilucoplan) as an add-on therapy for certain patients with generalised myasthenia gravis (gMG), a rare autoimmune disease with a global prevalence of 100 to 350 cases per one million people. The marketing authorisation, which specifically applies to adults who are anti-acetylcholine receptor (AChR) antibody-positive, makes Zilbrysq the first once-daily subcutaneous, targeted component 5 (C5) complement inhibitor for gMG. Patients with gMG can experience a variety of symptoms, including severe muscular weakness that can result in double vision, drooping eyelids, difficulty swallowing, chewing and talking, and life-threatening weakness of the muscles of respiration. UCB’s Zilbrysq inhibits complement-mediated damage to the neuromuscular junction through its targeted dual mechanism of action, the company said, adding that the therapy can be used simultaneously with intravenous immunoglobulin and plasma exchange without the need for supplemental dosing. The EC’s decision was supported by positive results from the late-stage RAISE study, which demonstrated that Zilbrysq delivered "rapid, consistent, clinically meaningful and statistically significant" improvements in patient- and clinician-reported outcomes at week 12 in a broad population of adult patients with mild-to-severe anti-AChR antibody-positive gMG, UCB said. The marketing authorisation comes less than two months after Zilbrysq was approved by the US Food and Drug Administration, also for adult gMG patients who are anti-AChR antibody-positive. Jean-Christophe Tellier, UCB’s chief executive officer, said: “With the EC’s approval of [Zilbrysq], I’m very excited that UCB is taking another important step forward in delivering patient value to the gMG community, giving clinicians an opportunity to address complement activation in gMG with a once-daily, self-administered, subcutaneous treatment option.” Beyond Zilbrysq, UCB’s neonatal Fc receptor (FcRn) blocker rozanolixizumab was recently recommended by the European Medicines Agency’s (EMA) human medicines committee as an add-on therapy for adults with gMG who are anti-AChR or anti-muscle-specific tyrosine kinase (MuSK) antibody-positive. If approved, 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. “Alongside a positive Committee for Medicinal Products for Human Use opinion from EMA for our FcRn blocker rozanolixizumab, and approvals for both [Zilbrysq] and rozanolixizumab in the US and Japan for the treatment of adults with gMG, our unique and differentiated portfolio of medicines reinforces our commitment to redefining treatment expectations for the gMG community,” Tellier said.