European Commission approves Nucala (mepolizumab) in three additional eosinophil-driven diseases

• Approval for the first targeted treatment for eosinophilic granulomatosis with polyangiitis and the first anti-IL-5 biologic treatment for patients with hypereosinophilic syndrome or chronic rhinosinusitis with nasal polyps in Europe
• Mepolizumab is now the only treatment approved in Europe for use in four eosinophil-driven diseases

GlaxoSmithKline (GSK) plc today announced that the European Commission has approved Nucala (mepolizumab), a monoclonal antibody that targets interleukin-5 (IL-5), for use in three additional eosinophil-driven diseases. This authorisation follows positive opinions recommended by the Committee for Medicinal Products for Human Use and authorises mepolizumab for use as an add on treatment in hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA) and chronic rhinosinusitis with nasal polyps (CRSwNP).

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. HES and EGPA are both potentially life-threatening rare diseases arising from inflammation in various tissues. The inflammation can cause a range of symptoms which are frequently severe. Mepolizumab is the first approved targeted treatment for EGPA and the first anti-IL-5 biologic treatment for patients with HES or CRSwNP in Europe. These approvals make mepolizumab the only treatment approved in Europe for use in four eosinophil-driven diseases as mepolizumab is already approved for use in Europe as an add-on treatment for patients aged six years and older with severe eosinophilic asthma (SEA).

Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK, said: “With millions of patients across Europe affected by eosinophil-driven diseases, we recognize the urgency in delivering the first approved targeted treatment for use in four of these conditions. Today’s approvals reinforce the important role treatments such as mepolizumab can play in helping to improve the lives of patients with these debilitating diseases.”

Individual country studies suggest that across Europe there are up to 22 million people who have CRSwNP. Patients with CRSwNP, particularly those with severe disease, may rely upon oral steroids to manage the inflammation and can require repeated surgical intervention due to recurrent growths to manage their condition. Advances in biologic therapies are providing options for these patients. Mepolizumab is now approved as an add-on therapy to intranasal corticosteroids for the treatment of adult patients with severe CRSwNP for whom therapy with systemic corticosteroids and/or surgery do not provide adequate disease control.

Available data suggest that across Europe, roughly 7000 people are affected by EGPA. EGPA is characterised by widespread inflammation in the walls of small blood vessels (vasculitis). The disease may affect multiple organ systems and be associated with symptoms of fatigue, muscle and joint pain and weight loss. The burden of disease may be high with patients experiencing recurrent relapses which prevent them from carrying out everyday activities. Currently, most patients with EGPA are treated with anti-inflammatory corticosteroids or immunosuppressive medicines (i.e. medicines that reduce the activity of the immune system) which can lead to both short and long-term adverse effects.  Mepolizumab is now approved as an add-on treatment for patients aged 6 years and older with relapsing-remitting or refractory EGPA.

Up to 5,000 adults in Europe are affected by HES. When eosinophils infiltrate certain tissues, they can cause inflammation which can lead to 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. The symptoms of HES may become progressively worse and can be life-threatening. HES can take many years to diagnose, and most patients continue to suffer from debilitating flares of their disease due to limited treatment options. Mepolizumab is now approved as an add-on treatment for adult patients with inadequately controlled HES without an identifiable non-haematologic secondary cause.

EGPA and HES are both rare diseases and epidemiological data is sparse, therefore the exact prevalence figures are unknown. It is probable that numbers of patients with EGPA and HES are underreported due to the rare nature of the conditions and delays in diagnosis.

Tonya Winders, CEO & President, Allergy and Asthma Network (AAN) and President of Global Allergy and Airways Patient Platform (GAAPP) commented: “The lives of patients affected by an eosinophil-driven disease are often impacted by what can be severe or life-threatening symptoms. They may rely on both intermittent or continuous oral steroids to manage their condition or be left feeling they have no option but to endure ongoing symptoms and possible flare-ups.   The availability of mepolizumab, a targeted biologic therapy, provides patients and their healthcare professionals with a new option in their armamentarium to treat hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and chronic rhinosinusitis with nasal polyps.”

The three 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:

• In patients with HES, significantly fewer patients (15 of 54 [28%] vs 30 of 54 [56%]; P = .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.
• In adult patients with EGPA, mepolizumab increased both accrued time in remission and proportion of patients achieving remission compared to placebo when added to standard of care.
• In adult patients with CRSwNP and at least one prior surgery, over 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, as well as reducing further surgeries up to week 52.

Epidemiological, clinical, and pathophysiological studies show that CRSwNP and asthma are closely linked and often coexist. Additionally, patients with EGPA usually also have asthma which can frequently be severe. This overlap across eosinophil-driven diseases underscores the importance of understanding the complex role of eosinophils in disease.

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.