China Clinical Trials Industry Development ConferenceClick for FreeRegistration
Note:This article does not constitute any investment opinions or suggestions., subject to official/company announcements;This article only introduces drugs related to medical health, not a recommendation of treatment options (if involved), and does not represent the platform's position.Any article reprinted needs to be authorized.
On September 9, the European Respiratory Society announced the detailed Phase III clinical data of the ultra-long-acting biologic Depemokimab published in The New England Journal of Medicine. Recently, GSK will communicate with the FDA to ensure a smooth approval for market launch.Depemokimab is the first ultra-long-acting biologic targeting interleukin-5 (IL-5) to be evaluated in a Phase 3 trial. IL-5 is a key cytokine in type 2 inflammation. More than 80% of severe asthma cases are driven by type 2 inflammation, characterized by elevated eosinophil levels and unpredictable exacerbations. By binding to IL-5, Depemokimab blocks its interaction with eosinophil surface receptors, inhibiting eosinophil biological activity and reducing their numbers to normal levels over time. This decreases eosinophil growth and the inflammation and tissue damage mediated by eosinophils, helping maintain a healthy state. The long half-life and high affinity of Depemokimab for IL-5 allow it to be administered once every six months for the treatment of severe asthma.On May 22, 2024, GSK announced that Depemokimab met the primary endpoint in two Phase III trials named SWIFT-1 and SWIFT-2. SWIFT-1 and SWIFT-2 are two identically designed randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase III clinical trials, with 375 and 380 patients enrolled respectively, lasting 52 weeks. These studies compared the therapy with placebo in adult and adolescent patients with severe asthma characterized by type 2 inflammation (marked by blood eosinophil count), aiming to evaluate the efficacy and safety of Depemokimab treatment. On September 9, the European Respiratory Society disclosed detailed Phase III data in The New England Journal of Medicine, showing a 54% reduction in severe exacerbations or severe asthma attacks among patients in the trial, and a 72% reduction in exacerbations requiring hospitalization or emergency department visits. In the SWIFT-1 trial, the annualized exacerbation rate with Depemokimab over 52 weeks was 0.46 compared to 1.11 for placebo. In SWIFT-2, these rates were 0.56 and 1.08, respectively. Compared with placebo, these studies achieved the primary goal of a statistically significant and clinically meaningful reduction in exacerbations over 52 weeks. In terms of safety, adverse events (AEs) occurred in 72-73% of patients in the Depemokimab group, compared to 73-78% in the placebo group, with AEs considered related to treatment accounting for 3-4% and 1-4%, respectively. Treatment discontinuation or withdrawal due to AEs occurred in 1% of the Depemokimab group versus 1-2% in the placebo group. No fatal AEs occurred in any study group. The proportion of patients experiencing nasopharyngitis AEs was lower in the Depemokimab group than in the placebo group.Severe asthma patients already have many marketed products to choose from. Currently, three IL-5 monoclonal antibody drugs have been approved globally. GSK's own Nucala (mepolizumab), the world’s first targeted human anti-interleukin-5 (IL-5) monoclonal antibody biologic, was initially approved by the FDA in 2015 for use with other asthma medications as a maintenance treatment for severe asthma patients aged 12 years and older; it was later approved by the U.S. FDA in September 2019 for pediatric patients aged 6 to 11 with severe eosinophilic asthma, making it the first biologic approved in the U.S. for treating this age group. In 2024, it was approved in China for the treatment of severe eosinophilic asthma. The dosage is 100 mg administered subcutaneously once every four weeks.In addition, other competitors of IL-5 monoclonal antibodies include Cinqair (reslizumab) from Teva Pharma.) and AstraZeneca's Fasenra (benralizumab). Cinqair was approved by the FDA in 2016 for the maintenance treatment of patients with severe asthma aged 18 years and older. The dosage and administration is 3 mg/kg intravenously once every 4 weeks. Fasenra was initially approved in 2017 as an add-on maintenance treatment for patients with severe eosinophilic asthma (SEA) aged 12 years and older. In 2024, it received approval from the US FDA as an add-on maintenance therapy to treat severe asthma in patients aged 6 to 11 with an eosinophilic phenotype. Fasenra is administered as a fixed-dose subcutaneous injection via a pre-filled syringe, with the first three doses given every 4 weeks, followed by once every 8 weeks.Kaivan Khavandi, Global Head of Respiratory/Immunology R&D at GSK, stated that real-world clinical data shows 40% of patients using these short-acting biologics discontinue treatment within a year. However, for a chronic condition like asthma, sustained suppression of inflammation and reduction in exacerbations are crucial. Treatment methods with a lighter burden, compared to frequent injections, are more likely to be accepted by patients. The uniqueness of Depemokimab lies in its high affinity for IL-5, enabling long-term inhibition of IL-5 activity. Ongoing Phase 3 clinical trials indicate that the drug requires only one subcutaneous injection every six months to help patients with severe eosinophilic asthma control their symptoms, significantly improving treatment adherence and durability. It has the potential to become the first long-acting biologic for treating severe eosinophilic asthma.Depemokimab's long half-life and high affinity for IL-5 imply sustained suppression of various inflammatory functions. Therefore, Depemokimab is currently undergoing Phase III trial evaluation in a range of other IL-5 mediated diseases, including OCEAN for Eosinophilic Granulomatosis with Polyangiitis (EGPA), ANCHOR for Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), and DESTINY for Hypereosinophilic Syndrome (HES). Additionally, another study (NIMBLE) is also underway to assess the efficacy and safety when patients with severe asthma switch from Mepolizumab or Benralizumab to Depemokimab.From a marketing perspective, faced with strong competitors like Teva Pharma and AstraZeneca, depemokimab is undoubtedly the best product to maintain GSK's leading position. If approved, the drug itself is expected to generate peak sales of £3 billion ($4 billion).Given the therapeutic advantages and economic benefits of IL-5 monoclonal antibody treatments, competition in China is becoming increasingly fierce. In 2022, GlaxoSmithKline (GSK)’s Depemokimab injection received clinical approval in China, with multiple indications entering Phase III clinical trials. In 2024, Mepolizumab was approved in China for the treatment of severe eosinophilic asthma. Currently, Bio-Thera Solutions' biosimilar of Mepolizumab is undergoing Phase I clinical trials in China. In March 2024, SSGJ-610, a recombinant anti-IL-5 humanized monoclonal antibody injection independently developed by 3SBio Inc., initiated Phase III clinical trials for treating severe asthma with elevated eosinophils, becoming the first domestically produced IL-5 monoclonal antibody to enter Phase III trials in China. In June 2024, Hengrui Medicine announced the results of the Phase I clinical trial (NCT04480762) of SHR-1703, a self-developed humanized anti-IL-5 monoclonal antibody. The results showed that SHR-1703 demonstrated superior safety and tolerability in healthy subjects, with a drug half-life of up to three months. Previous studies indicated that the average T1/2 of the marketed 250mg Mepolizumab is 17.9 to 20.4 days, while the average T1/2 of the investigational long-acting IL-5 monoclonal antibody Depemokimab (2mg~300mg) ranges from 37.6 to 52.5 days. This indicates that compared to both marketed and investigational IL-5 targeted drugs, SHR-1703 exhibits a significantly extended half-life, which could potentially prolong dosing intervals, reduce dosing frequency, and improve patient compliance. Among the development track of long-acting IL-5 antibodies, SHR-1703 ranks first in clinical progress in China and has the potential to become the Best-in-class drug in this field.Currently, the unit price of Mepolizumab entering China's medical insurance is 5,000 RMB per vial. Calculated on the basis of once every four weeks, the annual cost is 60,000 RMB. We look forward to the early launch of the long-acting Depemokimab to benefit patients as soon as possible. We also hope that other IL-5 monoclonal antibody clinical studies proceed smoothly, providing patients with more options.- 1. GSK to Approach FDA With
Positive Phase III Data For Long-Acting Asthma Med https://www.biospace.com/
- 2. Instructions for Each Product
Copyright Statement: This article is reproduced fromPharmaceutical Affairs纵横，Media or individuals who do not wish to be reproduced can contact us, and we will delete it immediately.
[About PharmaCircle]
PharmCube PRHub aims to assist biopharmaceutical technology enterprises in brand promotion and business development services. It provides systematic solutions based on customers' real needs, making brand information easily understandable to the public through "translation-simplification-contextualization." With access to over 1 million vertical users across various channels, it helps achieve collaboration goals, offering end-to-end marketing services from branding to business development for partners. We have successfully organized dozens of offline biopharmaceutical R&D conferences with 1,000 attendees, covering areas such as small-molecule new drugs, large-molecule new drugs, modified new drugs, and cross-border BD transactions, serving over a hundred listed/unicorn/biotech/pharmaceutical companies.
▲October 26-27, Chengdu