Ligelizumab

Chronic spontaneous urticaria is a skin condition characterised by persistent, itchy hives that last six weeks or longer. Credit: wisely via Shutterstock. The US Food and Drug Administration (FDA) has accepted for review the resubmitted supplemental Biologics License Application (sBLA) for Sanofi and Regeneron’s Dupixent (dupilumab) in chronic spontaneous urticaria (CSU). The application seeks to expand Dupixent’s use to treat adults and adolescents (aged 12 and older) with CSU inadequately controlled by H1 antihistamine therapy. The FDA’s target decision date is 18 April 2025. Dupixent, a fully human monoclonal antibody, inhibits the signalling of IL-4 and IL-13 pathways and is different from other immunosuppressants used to treat this condition. The resubmission builds on data from the LIBERTY-CUPID Phase III clinical trial (NCT04180488), which included three studies (Study A, Study B, and Study C). The sBLA adds pivotal results from Study C, conducted in biologic-naive patients with uncontrolled CSU who were receiving standard-of-care antihistamines. Study C met both its primary and key secondary endpoints, demonstrating that Dupixent significantly reduced itch and urticaria activity (hives and itch severity), aligning with earlier results from Study A. Safety data across the LIBERTY-CUPID programme were consistent with Dupixent’s established safety profile, with common adverse events including injection site reactions and Covid-19 infections. Dupixent has already been approved for CSU in Japan and the United Arab Emirates (UAE) and is under regulatory review in the European Union. Outside of Japan and the UAE, the safety and efficacy of Dupixent in CSU remain under evaluation. The potential new indication for CSU comes as Regeneron and Sanofi continue to expand Dupixent’s market presence. In September 2024, the FDA approved Dupixent for chronic obstructive pulmonary disease (COPD), marking its sixth indication and making it the first biologic approved for COPD. Dupixent is also approved for conditions including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis. Dupixent generated $11.3bn (€10.7bn) in global sales in 2023, as per Regeneron’s financials. Projections from GlobalData’s Pharma Intelligence Center suggest revenue could reach $23.6bn by 2030. GlobalData is the parent company of Pharmaceutical Technology. CSU is a skin condition characterised by persistent, itchy hives that last six weeks or longer. While antihistamines and anti-inflammatory treatments are used to manage symptoms, there is an unmet need for more effective options in patients with uncontrolled disease. Meanwhile, Novartis is advancing its CSU pipeline with promising data for its investigational drug, ligelizumab. Results from the Phase III study (NCT03907878) released in May 2024 showed that almost half of patients were completely free of itch and hives as assessed at week 52 using urticaria activity scores. Novartis said it plans to submit ligelizumab for regulatory approval in the second half of 2024.

SAN DIEGO, March 12, 2024 /PRNewswire/ -- Longbio Pharma (Suzhou) Co., Ltd. (referred to as "Longbio Pharma"), a leading biotech company dedicated to developing innovative protein treatments for allergy, respiratory, dermatology, hematology, ophthalmology, and other autoimmune and rare diseases, proudly announced the Phase I data of LP-003 (new generation of anti-IgE antibody) at the 2024 American Academy of Dermatology Association annual meeting (2024AAD). The presentation of the poster titled "A Phase 1 study in healthy subjects of LP-003, a novel long-acting, high affinity anti-IgE antibody" by Longbio Pharma marked a significant moment during the conference. Title: A Phase 1 study in healthy subjects of LP-003, a novel long-acting, high affinity anti-IgE antibody Abstract Submission ID: 50484 Presentation Time: Mar 8-12, 2024 Location: Poster Exhibits Center Results: In a randomized, double-blind, single-ascending-dose Phase I clinical study (CTR20221413), 32 healthy subjects were randomly divided into 5 groups to receive a single intravenous dose of 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 6 mg/kg and 10 mg/kg respectively. Safety, pharmacokinetics, and pharmacodynamics (free IgE levels) profile was evaluated. LP-003 exhibited a non-linear PK characteristic with T1/2 ranging from 44.6 days to 76.5 days, which is approximately 2～3 fold of Omalizumab. Moreover, the free-IgE was suppressed to below detection range for more than 168 days at 1 mg/kg group (except one with high baseline IgE level) to 10 mg/kg group. LP-003 appears to show good safety profile. No Grade 3 and above TEAE was reported, establishing a solid foundation for further investigation and advancement. Chronic spontaneous urticaria (CSU) stands as a prevalent skin disorder affecting approximately 1–2% of the global population. Despite SoC treatment, the efficacy and duration of relief remain significant challenges for patients and healthcare providers alike. Anti-IgE therapy was approved as a second-line treatment, however, only approximately 40% of patients achieving complete response following 300 mg Omalizumab dosing. Thus, a novel anti-IgE treatments offering higher efficacy and prolonged relief is needed. The successful Phase II study of Ligelizumab points a way that anti-IgE antibody with higher IgE affinity and more potent efficacy (FcεRI inhibition) retains the potential to be superior against Omalizumab. In this study, Longbio Pharma developed a new generation of anti-IgE antibody, LP-003, of higher IgE binding affinity, stronger FcεRI inhibition bioactivity, compared to Omalizumab and even Ligelizumab. Meanwhile, LP-003 has a much longer half-life (approximately 45∽76 days) compared to Omalizumab (approximately 17∽20 days). Moreover, a Phase II clinical trial (NCT06228560) of total 200 adult refractory CSU patients, despite up-dosing anti-histamine (H1) treatment, are being enrolled into 5 distinct groups (n=40/group), including three LP-003 treatment groups, one omalizumab treatment group, to provide a head-to-head comparison, and one placebo group. The topline results are expected to be released in early 2025. About LP-003 LP-003, a novel monoclonal anti-IgE antibody was generated, humanized, and engineered by Dr. Sun, Nai-chau, who is the inventor of Omalizumab, and co-founder of Tanox. Based on the 30+ years R&D experience on IgE target, Dr Sun developed a new generation of anti-IgE antibody (LP-003). Its extensive characterization including: affinity, bioactivity (FcεRI and FcεRII/CD23 inhibition), off-target binding and animal study (Tox and efficacy) was conducted. LP-003 just accomplished its Phase II study of allergic rhinitis. The current data shows LP-003 has the potential to become a best-in-class treatment. About Longbio Pharma LongBio Pharma is a biotech company located in Shanghai/Changshu, China. The company, which was founded in 2018, focuses on autoimmune and complement diseases, serving patients and society. For more information, please visit: or please contact: [email protected]. SOURCE Longbio Pharma