GSK Singapore announces regulatory approval for Nucala (mepolizumab) in two additional eosinophil-driven diseases
Approval as an add-on maintenance treatment for patients with severe Chronic Rhinosinusitis with Nasal Polyps and Hyper Eosinophilic Syndrome
Mepolizumab is now approved in Singapore for use in four eosinophil-driven diseases
SINGAPORE, Feb. 7, 2023 /PRNewswire/ -- GSK Singapore today announced that Nucala (mepolizumab), a monoclonal antibody that targets interleukin-5 (IL-5), has been approved for treatment in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and hypereosinophilic syndrome (HES). These new indications for mepolizumab are for the add-on maintenance treatment of severe CRSwNP in adult patients 18 years of age and older with inadequate response to nasal corticosteroids, and for adult patients with inadequately controlled HES without an identifiable non-haematologic secondary cause.
Eosinophil-driven diseases are inflammatory conditions associated with elevated levels of eosinophils, a type of white blood cell. CRSwNP is a condition in which patients develop soft tissue growths called nasal polyps which can cause chronic symptoms such as nasal obstruction, loss of smell and discharge. Globally, up to 90% of recurrent nasal polyps are characterised by high eosinophilic count, leading to repeated surgery. HES is a potentially life-threatening rare disease arising from inflammation in various tissues,. The inflammation can cause a range of symptoms which are frequently severe,. With the approvals, mepolizumab is now indicated across four eosinophilic-driven diseases, as mepolizumab is already approved for use in Singapore as an add-on treatment for patients aged 12 years and older with severe eosinophilic asthma (SEA), and for adult patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA).
Raakhi Sippy, Vice President and General Manager – GSK Singapore, said: "These approvals mark a significant chapter for patients in Singapore who are burdened by eosinophilic-driven diseases. To further the impact and help more patients, we are committed to exploring the role of IL-5 inhibition in eosinophil-driven diseases."
The approvals are based on data from pivotal trials investigating the role of targeted IL-5 inhibition with mepolizumab in these eosinophil-driven diseases. The studies demonstrated:
- SYNAPSE Study: All patients enrolled had at least one surgery, with 70% of whom also had a diagnosis of asthma. Mepolizumab demonstrated significant improvements in both the size of nasal polyps at the end of the 52-week study and in nasal obstruction during weeks 49-52, compared to placebo when added to standard of care. 50% (104/206) of the mepolizumab group achieved at least 1 point of improvement in nasal polyps score vs 28% (57/201) in the placebo; and 60% (124/206) of the mepolizumab group experienced more than 3 points improvement in nasal obstruction visual analogue score vs 36% (73/201) in the placebo. Also, there was a 57% reduction in the proportion of patients who had further surgeries in the group when treated with mepolizumab vs. placebo, HR=0.43 (95% CI 0.25, 0.76) up to week 52.
- FLARE Study: 50% fewer patients (15 of 54 [28%] vs 30 of 54 [56%]; P = 0.002) experienced a HES flare (worsening of symptoms or eosinophil threshold requiring an escalation in therapy) when treated with mepolizumab, compared to placebo, when added to standard of care treatment over the 32-week study period.
Professor Wang De Yun, Research Professor and Director of Research, Department of Otolaryngology – National University of Singapore, said: "Patients with eosinophil-driven disease often suffer from potentially severe or even life-threatening symptoms. To manage their condition, they would have to rely on oral steroids and recurrent surgeries. With the approval of mepolizumab for patients with CRSwNP and HES, they now have an alternative novel treatment option which could lighten their disease burden."
Through ongoing research, GSK is committed to improving the lives of those living with disease associated with uncontrolled eosinophilic inflammation, continuously innovating to address the unmet needs in this broad patient group.
CRSwNP is a chronic inflammatory disease of the nasal passage linings or sinuses which leads to soft tissue growths known as nasal polyps and is often characterised by elevated levels of eosinophils. The resultant swellings typically grow in both nostrils (bilateral) greatly impacting a patient due to various symptoms including nasal obstruction, loss of smell, facial pressure, and nasal discharge. Surgery may be indicated for severe cases. However, polyps have a strong tendency to reoccur often leading to repeat surgery.
HES is a rare and under-diagnosed disorder, making it difficult to estimate its overall prevalence. Patients with HES have a persistent and marked overproduction of eosinophils, a type of white blood cell. When eosinophils infiltrate certain tissues, they can cause inflammation and organ damage which, over time, can impact patients' day-to-day ability to function. Complications can range from fever and malaise to respiratory and cardiac problems. If left untreated, the symptoms of HES become progressively worse, and the disease can be life-threatening.
About Nucala (mepolizumab)
First approved in 2015 for SEA, Nucala (mepolizumab) is the first-in-class monoclonal antibody that targets IL-5. It is believed to work by preventing IL-5 from binding to its receptor on the surface of eosinophils, reducing blood eosinophils and maintaining them within normal levels. The mechanism of action for mepolizumab has not been definitively established.
Mepolizumab has been developed for the treatment of diseases that are driven by inflammation caused by eosinophils. It has been studied in over 4,000 patients in 41 clinical trials across several eosinophilic indications and has been approved in the US, the EU and in over 25 other markets, as an add-on maintenance treatment for patients with SEA. Mepolizumab is approved in 17 markets, including the EU and US, for paediatric use in SEA from ages six to 17 years of age, with approval in an additional seven markets for use in patients with SEA aged 12-17 years. The first approval for mepolizumab in CRSwNP was granted by the FDA in July 2021. Mepolizumab is approved for use in patients with EGPA in a total of 14 markets including the US, Japan and Canada. Mepolizumab was first approved for use in HES in the US in September 2020 and approvals have since then been granted in an additional 5 markets. Mepolizumab is currently in clinical development for chronic obstructive pulmonary disorder (COPD), and it is not currently approved for use in COPD anywhere in the world.
Important Safety Information
The following information is based on the Singapore Prescribing Information for Nucala in licensed indications only. Please consult the full Prescribing Information for all the labelled safety information for Nucala.
Nucala should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.
WARNINGS AND PRECAUTIONS
- Nucala should not be used to treat acute asthma exacerbations.
- Asthma-related adverse events or exacerbations may occur during treatment with Nucala. Patients should be instructed to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with Nucala.
- Abrupt discontinuation of corticosteroids after initiation of Nucala therapy is not recommended. Reductions in corticosteroid doses, if required, should be gradual and performed under the supervision of a physician.
- Nucala treated patients may experience a return of EGPA symptoms upon cessation of Nucala. As patients may decrease their other EGPA treatments during treatment with Nucala, if Nucala treatment is discontinued then other EGPA treatments may need to be increased accordingly.
- Acute and delayed systemic reactions, including hypersensitivity reactions (e.g. anaphylaxis, urticaria, angioedema, rash, bronchospasm, hypotension), have occurred following administration of Nucala. These reactions generally occur within hours of administration, but in some instances had a delayed onset (i.e.days). These reactions may occur for the first time after a long duration of treatment.
- Eosinophils may be involved in the immunological response to some helminth infections. Patients with pre-existing helminth infections were excluded from participation in the clinical programme. Patients with pre-existing helminth infections should be treated for their infection prior to Nucala therapy. If patients become infected whilst receiving treatment with Nucala and do not respond to anti-helminth treatment, temporary discontinuation of Nucala should be considered.
- Nucala has not been studied in patients with life-threatening manifestations of HES.
Headache was very common (incidence ≥10%) in severe asthma clinical trials. Common adverse reactions (incidence ≥1% to <10%) included headache, back pain and injection site reaction. Injection site reactions (e.g. pain, erythema, swelling, itching, burning sensation) occurred in 8% of subjects treated with 100 mg of Nucala versus 3% treated with placebo.
In a clinical trial in patients with EGPA receiving 300 mg of Nucala, no additional adverse reactions were identified to those reported in severe asthma clinical trials. Injection site reactions (e.g. pain, erythema, swelling) occurred in 15% of subjects treated with 300 mg of Nucala versus 13% treated with placebo.
In a clinical trial in patients with HES, no additional adverse reactions were identified to those reported in the severe asthma trials.
In a clinical trial with CRSwNP, no additional adverse reactions were identified to those reported in the severe asthma trials.
GSK's commitment to respiratory disease
For over 50 years, GSK has led the way in developing medicines that advance the management of asthma and COPD. From introducing the world's first selective short-acting beta agonist in 1969, to launching six treatments in five years to create today's industry-leading respiratory portfolio, we continue to innovate so we can reach the right patients, with the right treatment. Working together with the healthcare community, we apply world-class science to discover and understand the molecules that become the medicines of tomorrow. We won't stand still until the simple act of breathing is made easier for everyone.
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/company.
Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described in the Company's Annual Report on Form 20-F for 2021, GSK's Q4 Results for 2022 and any impacts of the COVID-19 pandemic.
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Singapore Nucala Prescribing Information, October 2022
Pavord ID, Bel EH, Bourdin A, et al. From DREAM to REALITI-A and beyond: Mepolizumab for the treatment of eosinophil-driven diseases. Allergy. 2021 Aug;77(3):717-1074
Han JK, Bachert C, Fokkens W, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021 Oct;9(10):1141-1153
Lou H, Meng Y, Piao Y, et al. Cellular phenotyping of chronic rhinosinusitis with nasal polyps. Rhinology. 2016 Jun;54(2):150-9
Roufosse F, Kahn J-E, Rothenberg ME, et al. Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020 Dec;146(6):1397-1405
Nucala (mepolizumab) Summary of Product Characteristics available at https://www.ema.europa.eu/en/documents/product-information/nucala-epar-product-information_en.pdf (Last accessed January 2023)
SOURCE GSK Singapore