Chronic rhinosinusitis with nasal polyps

GSK’s Nucala was approved in the US for severe asthma with an eosinophilic phenotype treatment. Credit: MAXSHOT.PL / Shutterstock. The China National Medical Products Administration (NMPA) has approved GSK’s Nucala (mepolizumab) as an add-on treatment with intranasal corticosteroids to treat chronic rhinosinusitis with nasal polyps (CRSwNP) in the adult population. This marks the third indication for an interleukin-5 (IL-5) targeting monoclonal antibody, Nucala, in the region for an IL-5 mediated condition. The approval of the antibody offers an alternative for those who find systemic corticosteroids and surgery ineffective. The decision by the NMPA is underpinned by the Phase III MERIT trial outcomes, which included subjects from China, Russia, and Japan and is supported by the global Phase III SYNAPSE study. GSK Respiratory/Immunology R&D global head and SVP Kaivan Khavandi said: “We are delighted that Nucala has been approved in China as a treatment for CRSwNP, a chronic condition for which new and effective treatments are needed. “Patients now have a non-surgical option available to them and an alternative to repeated exposure to oral corticosteroids.” The MERIT trial assessed the safety and efficacy of the therapy for 52 weeks against a placebo. The change from baseline in nasal obstruction visual analogue scale (VAS) score and endoscopic nasal polyp score at week 52 was the co-primary endpoint. According to the findings from 163 trial subjects, it is determined that the therapy ‘significantly improved’ nasal obstruction VAS score and reduced nasal polyp score. Previously approved in China for severe eosinophilic asthma in adult and adolescent individuals of 12 years of age and above, and adults with eosinophilic granulomatosis with polyangiitis, the therapy was also granted approval in the US in 2015 for severe asthma with an eosinophilic phenotype. Chronic rhinosinusitis is a prevalent condition in China, affecting an estimated 107 million people. Approximately one-third of these individuals suffer from this condition, the company noted. Often associated with type 2 inflammation, CRSwNP is characterised by high levels of IL-5 in nasal polyp tissue and a tendency for nasal polyps to regrow post-surgery due to persistent inflammation.

GSK’s blockbuster respiratory drug Nucala has secured a China label expansion for certain patients with inflamed sinuses. But a more important challenge on the way to hitting its multibillion-dollar peak sales projections is on the horizon. Nucala could reach $2.35 billion in 2026 sales, according to GlobalData analysts. But this sky-high forecast is mainly driven by a potential new expansion in chronic obstructive pulmonary disease — the third leading cause of death worldwide. Late-stage data are still yet to be detailed, but a PDUFA date is set for May 7. On Friday, China’s NMPA greenlit the drug as an add-on to intranasal corticosteroids for people with chronic rhinosinusitis with nasal polyps (CRSwNP) that are inadequately controlled. The approval marks the third indication for Nucala in the country, following previous green lights for severe asthma and eosinophilic granulomatosis with polyangiitis. There are around 30 million people in China with CRSwNP, according to GSK. The latest approval gives them an alternative option to surgery and repeat use of oral corticosteroids, GSK’s head of respiratory and immunology R&D Kaivan Khavandi said in a release. Nucala is also approved for CRSwNP in the US, alongside other indications including severe asthma, hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis. The product reached £444 million ($550 million) in sales in the third quarter of 2024. While Nucala’s market expansion in China is welcome, the bigger commercial focus for GSK is COPD. In September, Nucala passed a Phase 3 test for the disease, which affects more than 390 million people worldwide. The drugmaker has yet to share details of the data publicly, but has already submitted them to the FDA. In December, CEO Emma Walmsley told investors at the Redburn Atlantic CEO Conference that Nucala could become “the first once-monthly biologic proven to reduce exacerbations across the full spectrum of COPD patients.” And “that’s important when you look at the competitive context here because we have included the most difficult-to-treat patients – those with emphysema, which I think is about a third of the market,” she added. Elsewhere, the company also has an ultra-long acting anti-IL-5 candidate, depemokimab, which is set to enter Phase 3 development for COPD this year. The drug has the potential to be efficacious when administered as little as once every six months, offering more convenience for patients.

According to information from the CDE website, GlaxoSmithKline (GSK) has submitted a marketing application for depemokimab in China. Considering the latest progress in clinical trials, the expected indication for this drug is severe eosinophilic asthma (SEA). Depemokimab is a new generation anti-interleukin 5 (IL-5) monoclonal antibody developed by GSK, characterized by a longer half-life, high binding affinity, and high potency, requiring only one injection every six months. In contrast, GSK's first-generation IL-5 monoclonal antibody, mepolizumab (trade name: Nucala), requires monthly injections and was approved for marketing in the United States in November 2015. According to GSK's financial report, global sales of mepolizumab were approximately $2 billion in 2023. Currently, depemokimab has completed four Phase III clinical studies targeting SEA and chronic rhinosinusitis with nasal polyps (CRSwNP). Two Phase III studies for SEA (SWIFT-1 and SWIFT-2) showed a significant reduction in the frequency of asthma attacks in the depemokimab group compared to the placebo group after 52 weeks of treatment. Similarly, two Phase III studies for CRSwNP (ANCHOR-1 and ANCHOR-2) also indicated a significant decrease in the total nasal endoscopic polyp score in the depemokimab group compared to the placebo group after 52 weeks of treatment. Additionally, the nasal congestion scores in the depemokimab group, assessed through a verbal rating scale (VRS) during weeks 49-52, also showed a significant reduction compared to the placebo group. Detailed data has not been publicly disclosed yet.