Chronic rhinosinusitis with nasal polyps

Dupixent significantly reduced itch and hive activity from baseline; 41% of patients achieved well-controlled disease status Confirmatory data to support U.S. regulatory resubmission by year-end; if approved, Dupixent would be the first new targeted treatment for people living with chronic spontaneous urticaria in more than 10 years More than 300,000 people in the U.S. suffer from chronic spontaneous urticaria that is inadequately controlled by antihistamines Oct. 24, 2024 -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi will present positive data from the Phase 3 LIBERTY-CUPID Study C evaluating the investigational use of Dupixent® (dupilumab) in biologic-naïve patients with uncontrolled chronic spontaneous urticaria (CSU) who receive background therapy with antihistamines. Results showed treatment with Dupixent significantly reduced itch and urticaria activity (itch and hive) scores from baseline, and a higher proportion of patients achieved well-controlled disease status compared to placebo. The data are being shared in a late-breaking oral presentation at the American College of Allergy, Asthma & Immunology (ACAAI) 2024 Annual Scientific Meeting in Boston, Massachusetts. “Chronic spontaneous urticaria is an inflammatory skin condition that affects patients with unpredictable episodes of intense itching and hives, often severely impacting their daily lives," said Thomas B. Casale, M.D., Professor, Internal Medicine, Morsani College of Medicine at the University of South Florida, USA. "These data confirm results seen in the previous Study A and reinforce the potential of Dupixent to significantly alleviate symptoms for patients, helping them to better control this challenging disease.” Study C enrolled 151 children and adults who were randomized to receive Dupixent (n=74) or placebo (n=77) added to standard-of-care histamine-1(H1) antihistamines. At 24 weeks, Dupixent demonstrated significant improvements compared to placebo on: Itch severity score (8.64- vs. 6.10-point reduction from baseline; p=0.02) Urticaria (itch and hive) activity score (15.86- vs. 11.21-point reduction from baseline; p=0.02). Well-controlled disease status (urticaria activity score ≤6; 41% vs. 23%; p=0.005) Complete response (urticaria activity score=0; 30% vs. 18%; p=0.02) The safety results in Study C were generally consistent with the known safety profile of Dupixent in its approved dermatological indications. Overall rates of treatment emergent adverse events (AEs) were 53% for both Dupixent and placebo. AEs more commonly observed with Dupixent (≥5%) compared to placebo included injection site reactions (12% vs. 4%), accidental overdose (7% vs. 3%) and COVID-19 infection (8% vs. 5%). Dupixent has been approved for CSU in Japan and the United Arab Emirates (UAE) and is also under regulatory review in the European Union based on earlier trial readouts. Outside of Japan and the UAE, the safety and efficacy of Dupixent for CSU has not been fully evaluated by any regulatory authority. CSU is a chronic inflammatory skin disease driven in part by type 2 inflammation, which causes sudden and debilitating hives and persistent itch. CSU is typically treated with H1 antihistamines, medicines that target H1 receptors on cells to control symptoms of urticaria. However, the disease remains uncontrolled despite antihistamine treatment in many patients, some of whom are left with limited alternative treatment options. These individuals continue to experience symptoms that can be debilitating and significantly impact their quality of life. More than 300,000 people in the U.S. suffer from CSU that is inadequately controlled by antihistamines. The LIBERTY-CUPID Phase 3 program evaluating Dupixent for CSU consists of Study A, Study B and Study C. Study C was a randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of Dupixent as an add-on to standard-of-care antihistamines compared to antihistamines alone in 151 patients aged six years and older with CSU who remained symptomatic despite antihistamine use and were not previously treated with omalizumab (i.e., biologic-naïve). The primary endpoint assessed the change from baseline in itch at 24 weeks (measured by the weekly itch severity score [ISS7], 0-21 scale). Secondary endpoints at 24 weeks, measured by the weekly urticaria activity score (UAS7), included the change from baseline in itch and hives (UAS7, 0-42 scale), proportion of patients achieving well-controlled disease status (UAS7 ≤6), and complete response (UAS7=0). Dupixent, which was invented using Regeneron’s proprietary VelocImmune® technology, is a fully human monoclonal antibody that inhibits the signaling of the IL-4 and IL-13 pathways and is not an immunosuppressant. The Dupixent development program has shown significant clinical benefit and a decrease in type 2 inflammation in Phase 3 trials, establishing that IL-4 and IL-13 are two of the key and central drivers of type 2 inflammation that play a major role in multiple related and often co-morbid diseases. Dupixent has received regulatory approvals in more than 60 countries in one or more indications including certain patients with atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, CSU, and chronic obstructive pulmonary disease in different age populations. More than 1,000,000 patients are being treated with Dupixent globally. Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved or authorized fully human monoclonal antibodies. This includes REGEN-COV® (casirivimab and imdevimab), Dupixent, Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb), Inmazeb® (atoltivimab, maftivimab and odesivimab-ebgn) and Veopoz™ (pozelimab-bbfg). Dupilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement. To date, dupilumab has been studied across more than 60 clinical trials involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation. In addition to the currently approved indications, Regeneron and Sanofi are studying dupilumab in a broad range of diseases driven by type 2 inflammation or other allergic processes in Phase 3 trials, including chronic pruritus of unknown origin and bullous pemphigoid. These potential uses of dupilumab are currently under clinical investigation, and the safety and efficacy in these conditions have not been fully evaluated by any regulatory authority. Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases. Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases. We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions. 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LONDON, UK I October 14, 2024 I GSK plc (LSE/NYSE: GSK) today announced positive headline results from the phase III clinical trials ANCHOR-1 and ANCHOR-2, which assessed the efficacy and safety of depemokimab versus placebo in adults with CRSwNP. Both trials met their co-primary endpoints of a change from baseline in total endoscopic nasal polyp score at 52 weeks and change from baseline in mean nasal obstruction score from weeks 49 to 52. The overall incidence and severity of treatment-emergent adverse events across both trials were similar in patients treated with either depemokimab or placebo. Further analysis of these data is ongoing. The full results of ANCHOR-1 and ANCHOR-2 will be presented at an upcoming scientific congress. Kaivan Khavandi, SVP, Global Head of Respiratory/Immunology R&D at GSK, said: “Globally millions of people suffer from uncontrolled CRSwNP, the majority of whom will exhibit markers of type 2 inflammation. These patients have high corticosteroid exposure and often experience recurrence of nasal polyps following surgery. We’re very encouraged by the results from the ANCHOR studies, which demonstrate the potential for depemokimab to offer targeted and sustained suppression of a key inflammatory pathway underlying nasal polyp growth and nasal obstruction. Today’s data, along with recent phase III data in severe asthma, will be used in regulatory filings around the world.” Depemokimab is the first ultra-long-acting biologic to be evaluated in phase III trials with an extended half-life and high binding affinity and potency for interleukin-5 (IL-5), which could enable dosing once every six-months for patients with CRSwNP. 1-3 IL-5 is present at high levels in nasal polyp tissue and is a key cytokine (protein) in type 2 inflammation. 1,4-7 These data are part of GSK’s aspirations to advance treatment goals for those with type 2 inflammatory conditions like CRSwNP. Being able to deliver sustained suppression of inflammation that drives the disease and its progression, has the potential to benefit patients and clinicians by reducing the risk of inflammation reoccurring due to missed doses. Increased dosing intervals may also reduce the need for regular clinic time. CRSwNP is a chronic condition that affects up to 4% of the general population, of whom 40% have uncontrolled disease. 8,9 It is caused by inflammation of the nasal lining that can lead to soft tissue growths, known as nasal polyps. 4,10 People with CRSwNP experience symptoms such as nasal obstruction, loss of smell, facial pressure, sleep disturbance, infections and nasal discharge that can significantly affect their emotional and physical well-being. 4,10 Up to 80% of people with CRSwNP show evidence of type 2 airway inflammation, typically detected by blood eosinophil count as a biomarker, which is associated with more severe disease and symptoms. 4-7,11 These patients are likely to have a history of sinonasal surgery, which is accompanied by a high risk of nasal polyp recurrence and have high OCS use that is known to be associated with severe complications. 7,10,11 Data from ANCHOR-1 and ANCHOR-2 along with data from SWIFT-1 and SWIFT-2, the phase III trials of depemokimab in severe asthma, will be used  in regulatory filings around the world. Depemokimab is currently not approved anywhere. About ANCHOR-1 and ANCHOR-2 1,2 ANCHOR-1 and ANCHOR-2 were replicate phase III clinical trials assessing the safety and efficacy of depemokimab in patients with CRSwNP. Both were 52-week, randomised, double-blind, parallel group, placebo controlled, multi-centre trials. Number of subjects included in the Full Analysis Set of ANCHOR-1: depemokimab = 143, placebo = 128 and in ANCHOR-2: depemokimab = 129, placebo = 128. About the depemokimab development programme Depemokimab’s extended half-life, high potency and high binding affinity for IL-5 means it has the potential to provide sustained inhibition of broad inflammatory functions with dosing once every six-months. The phase III programme includes evaluation of depemokimab in other IL-5 mediated diseases. These include severe asthma, 3,13,14 eosinophilic granulomatosis with polyangiitis (EGPA) 14 and hypereosinophilic syndrome (HES). 15 The first phase III trials in severe asthma, SWIFT-1 and SWIFT-2, have been reported and published in the New England Journal of Medicine. 3 GSK in respiratory GSK continues to build on decades of pioneering work to deliver more ambitious treatment goals, develop the next generation standard of care, and redefine the future of respiratory medicine for hundreds of millions of people with respiratory diseases. With an industry-leading respiratory portfolio and pipeline of vaccines, targeted biologics, and inhaled medicines, we are focused on improving outcomes and the lives of people living with all types of asthma and COPD along with less understood refractory chronic cough or rarer conditions like systemic sclerosis with interstitial lung disease. GSK is harnessing the latest science and technology with the aim to modify underlying disease dysfunction and prevent disease progression. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. References SOURCE: GlaxoSmithKline

GSK announced another batch of positive data from its respiratory program with the investigational drug depemokimab, this time in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Both the Phase 3 ANCHOR-1 and ANCHOR-2 trials met the co-primary endpoints: the total endoscopic nasal polyp score at 52 weeks and mean nasal obstruction score from weeks 49 to 52. Treatment-emergent adverse events in the trials were similar in patients treated with either the drug or placebo, the UK-based company said, explaining its potential long-acting option can be dosed once every six months. Data from the trials will be used in regulatory filings globally, GSK’s SVP and global head of respiratory and immunology R&D Kaivan Khavandi said . “These patients have high corticosteroid exposure and often experience recurrence of nasal polyps following surgery,” Khavandi said in a statement. He added that the data “demonstrate the potential for depemokimab to offer targeted and sustained suppression of a key inflammatory pathway underlying nasal polyp growth and nasal obstruction.” CRSwNP is a chronic condition that is caused by inflammation of the nasal lining and can lead to nasal polyps, along with other symptoms like loss of smell and pressure in the face. It affects up to 4% of the general population, and executives have said that if depemokimab, which targets interleukin-5 (IL-5), is approved, they expect it to reach £3 billion ($3.9 billion) in peak annual sales. This is the second batch of data from trials with depemokimab in as many months: In September , GSK released data showing that depemokimab reduced asthma attacks by 54% in two large Phase 3 trials, though the studies did miss statistical significance on secondary endpoints assessing quality-of-life and symptom-based measures.