EMA OKs Nucala for Severe Refractory Eosinophilic Asthma

Troy Brown, RN


December 03, 2015

The European Medicines Agency (EMA) has approved mepolizumab (Nucala, GlaxoSmithKline) as an add-on treatment for severe refractory eosinophilic asthma in adults in the 31 European countries covered by the EMA, according to a company statement.

Mepolizumab will be the first anti-interleukin-5 (IL-5) treatment for these patients in the European Union. IL-5 is important in regulating eosinophil regulation in patients with asthma. Mepolizumab is given as a subcutaneous injection of 100 mg every 4 weeks in addition to the patient's usual respiratory medications, which often include high-dose inhaled corticosteroids and additional medicines that may include oral corticosteroids.

Approximately 242 million individuals worldwide live with asthma. Existing therapies provide relief for many of these patients, but fewer than 5% of patients have severe refractory treatment that is not controlled with existing treatments.

Severe asthma requires medication with high-dose inhaled corticosteroids and the addition of a second controller (and/or systemic corticosteroids) to prevent the asthma from becoming uncontrolled or remaining uncontrolled despite the use of these medications. These patients may need long-term oral corticosteroids.

In severe eosinophilic asthma, the overproduction of eosinophils causes lung inflammation that can affect the airways, restricting respiration and increasing the frequency of asthma attacks.

IL-5 is the main stimulator of eosinophilic growth, activation, and survival, and promotes eosinophil movement from the bone marrow into the lung. As many as 60% of those with severe asthma have eosinophilic airway inflammation.

Mepolizumab is a monoclonal antibody that prevents IL-5 from binding to its receptor on the surface of eosinophils. This binding reduces eosinophil levels in the blood, tissue, and sputum.

"Not the Typical 'Asthma' Patients"

"Patients with severe refractory eosinophilic asthma are not the typical 'asthma' patients many people are familiar with. Despite taking high doses of inhaled medications, they struggle to control their asthma," lead investigator of the first proof-of-concept trial for mepolizumab and an investigator for the phase 3 MENSA study, Professor Ian Pavord, DM, FRCP, from the University of Oxford, commented in the news release.

"They have particular problems with frequent asthma attacks and can require hospitalisation. Many also take oral corticosteroids to control their symptoms, which we know can lead to side effects that patients often find very difficult to deal with. To be able to offer these patients a treatment that specifically targets the underlying cause of their disease will be an important option," he said.

The phase 2 and phase 3 trials included nine studies with a total of 915 participants with severe refractory eosinophilic asthma who were given either a subcutaneous or an intravenous dose of mepolizumab during clinical trials lasting 24 to 52 weeks. Those three clinical trials (DREAM [MEA112997], MENSA [MEA115588], and SIRIUS [MEA115575]) found mepolizumab to be efficacious and safe for those patients with severe refractory eosinophilic asthma.

The trials studied the efficacy and safety of mepolizumab in those with severe asthma. All participants in the MENSA and SIRIUS studies had eosinophil levels in their peripheral blood of at least 150 cells/μL at the beginning of treatment, or at least 300 cells/μL in the previous year.

A summary of product characteristics is available on the European Commission's website.

The US Food and Drug Administration approved Nucala on November 4, 2015, as an add-on treatment for patients aged 12 years and older with severe eosinophilic asthma.

Other countries, including Japan, have submitted regulatory applications that are under review.

Mepolizumab is contraindicated in those with hypersensitivity to mepolizumab or any of its excipients. It should not be used for treatment of acute asthma exacerbations.

Adverse events usually occur within hours of admission, but can be delayed. They include acute and delayed systemic reactions, including hypersensitivity reactions (eg, urticaria, angioedema, rash, bronchospasm, and hypotension). Patients who experience any of these events or whose asthma worsens or remains uncontrolled after beginning treatment should seek medical advice.

The most frequent reported events in the clinical studies of patients with severe refractory eosinophilic asthma were headache, injection site reactions, and back pain. Headaches were very common, occurring in at least one of every 10 patients. Other common adverse events included lower respiratory tract infection, urinary tract infection, pharyngitis, hypersensitivity reactions (systemic, allergic), nasal congestion, upper abdominal pain, eczema, back pain, administration-related reaction (systemic, nonallergic), local injection site reactions, and pyrexia.

Do not discontinue mepolizumab or corticosteroids abruptly; discontinuing or reducing corticosteroids should be gradual and occur only under the supervision of a physician.


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