IL-5

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.

The blockbuster Sanofi and Regeneron Pharmaceuticals drug Dupixent, already commercialized in several skin and lung disorders, has expanded its FDA-approval to chronic obstructive pulmonary disease (COPD), a progressive lung condition prevalent in smokers. The regulatory decision announced Friday permits Dupixent’s use as an add-on maintenance treatment of adults whose COPD is inadequately controlled by available therapies. The every-other-week injectable drug is now the first biologic therapy approved by the FDA for treating COPD. In COPD, damage to the lungs leads to inflamed airways that cause breathing difficulty, coughing, and wheezing. The disease can be caused by long-term exposure to inhaled irritants, which is why it’s prevalent in smokers. But non-smokers can also develop COPD. Standard treatment includes drugs and drug combinations that widen airways and reduce inflammation. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum Dupixent is an antibody designed to block IL-13 and IL-4, two signaling pathways that drive inflammation. In COPD, the drug is intended to specifically address type 2 inflammation, an excessive immune response characterized by accumulation of certain immune cells in tissue. Dupixent’s FDA approval in COPD covers the drug’s use to treat patients whose disease is driven by immune cells called eosinophils. The FDA approval in COPD is based on results from two Phase 3 tests that compared the drug to a placebo in adults who were currently receiving standard-of-care inhaled therapy. Results for both studies showed statistically significant reductions in the annualized rate of moderate or severe COPD exacerbations measured over one year. Dupixent has been developed under a partnership between Sanofi and Regeneron, who share in profits from the drug. Sanofi recognizes all revenue from antibodies in the partnership. The drug accounted for €10.7 billion (about $11.6 billion) in sales in 2023, up nearly 30% from the prior year, according to the pharma giant’s annual report. Dupixent gives Sanofi a pipeline in a product opportunity, Paul Rowe, Sanofi’s head of medical affairs specialty care North America, said in an interview ahead of the FDA decision. The drug was first approved in 2017 for treating for atopic dermatitis followed by asthma in 2018. With the latest FDA nod, the drug can now treat six respiratory and dermatological conditions. “Given success we’ve had in these other disorders, we think there’s a strong rationale for COPD as well,” Rowe said. Sponsored Post Get Ready for HLTH 2024: A Preview Guide HLTH 2024, scheduled for October 20-23 at the Venetian Expo Center in Las Vegas, will highlight new programming, a physicians roundtable, generative AI, the shifting landscapes of telemedicine, retail health, women's health, and lots more. By Stephanie Baum COPD treatment has mainly consisted of older drugs, mostly inhaled therapies, but that’s changing. In June, the FDA approved Verona Pharma’s Ohtuvayre, an inhalable drug that hits two targets, one to counteract inflammation and the other to open up airways. Dupixent could also face new biologic competition. Nucala, a GSK antibody that blocks the IL-5 pathway, recently posted positive Phase 3 data in a COPD study. The results could represent a comeback for Nucala, which the FDA rejected for COPD in 2018. The injectable GSK drug is currently approved for treating asthma. An FDA decision for Dupixent in COPD was initially expected in June. But in May, the agency notified the company it needed more time to review additional clinical data it had requested. In a separate Friday decision, regulators in China approved Dupixent for COPD, Sanofi and Regeneron said. Dupixent’s first approval in COPD was in Europe, a regulatory decision handed out in July.