GSK Nucala (mepolizumab) filings accepted by European Medicines Agency for three additional eosinophil-driven diseases

For media and investors only

Issued: London, UK

  • Submissions based on positive data from pivotal studies in hypereosinophilic syndrome, chronic rhinosinusitis with nasal polyps and eosinophilic granulomatosis with polyangiitis
  • If approved in the EU, Nucala would be the only treatment indicated for four eosinophil-driven diseases

GlaxoSmithKline plc (GSK) today announced that the European Medicines Agency (EMA) has accepted regulatory submissions seeking approval for the use of anti-IL5 biologic Nucala (mepolizumab) in three additional conditions: hypereosinophilic syndrome (HES), chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic granulomatosis with polyangiitis (EGPA).

Nucala is currently approved for use in Europe as an add-on treatment for patients with severe eosinophilic asthma. If the submissions are approved, it would be the only treatment indicated for use in four eosinophil-driven diseases in Europe, the first biologic approved for HES and the first treatment of any kind approved for EGPA.

Eosinophil-driven diseases such as severe eosinophilic asthma, HES, CRSwNP and EGPA are inflammatory conditions characterised by raised eosinophil levels. HES and EGPA are both rare diseases which can be life-threatening, and patients currently have limited treatment options. Nasal polyps can cause chronic symptoms such as nasal obstruction and discharge. Patients with severe disease may require surgical intervention, however polyps can recur meaning patients go through repeated surgeries that become progressively less effective and riskier.

Reducing blood eosinophils to normal levels with targeted treatment has shown benefits across a range of eosinophil-driven diseases. The three submissions are based on results from a series of pivotal studies which demonstrated:

  • In patients with HES, significantly fewer patients experienced a HES flare (worsening of symptoms or eosinophil threshold requiring an escalation in therapy) over the 32-week study period when treated with Nucala compared to placebo when added to standard of care.
  • In patients with CRSwNP and at least one prior surgery, Nucala 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.
  • In patients with EGPA, Nucala increased both accrued time in remission and proportion of patients achieving remission compared to placebo when added to standard of care.

Global submissions for these additional indications are ongoing. Nucala is not approved for use in nasal polyps anywhere in the world. It is not approved for use in HES or EGPA in the EU.

About Hypereosinophilic Syndrome (HES)

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. People with HES may have eosinophil levels three times greater than normal. 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 chronic rhinosinusitis with nasal polyps (CRSwNP)

CRSwNP is a chronic inflammatory disease of the nasal passage linings or sinuses leading to soft tissue growth known as nasal polyps in the upper nasal cavity and is characterised by elevated levels of eosinophils. The resultant swellings can grow in both nostrils (bilateral) greatly impacting a patient’s quality of life due to nasal obstruction, loss of smell, facial pain, facial pressure and nasal discharge. Surgery to remove the polyp tissue may be indicated for severe cases. However, polyps have a strong tendency to reoccur often leading to repeat surgery. 

About eosinophilic granulomatosis with polyangiitis (EGPA)

EGPA is a chronic rare disease that is caused by inflammation in the walls of small-to-medium sized blood vessels (vasculitis). In EGPA, patients typically develop adult-onset asthma, and often allergic rhinitis and sinusitis. EGPA can result in damage to lungs, sinuses, skin, heart, gastrointestinal tract, nerves and other organs and can be life-threatening for some patients. The most common symptoms include extreme fatigue, muscle and joint pain, weight loss, sinonasal symptoms, and breathlessness.

About mepolizumab

First approved in 2015 for severe eosinophilic asthma (SEA), 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 to normal levels. At normal levels eosinophils play a role in maintaining health.

Mepolizumab has been developed for the treatment of diseases that are driven by inflammation caused by eosinophils. It has been studied in over 3,000 patients in 26 clinical trials across a number of eosinophilic indications and has been approved under the brand name Nucala in the US, Europe and in over 20 other markets, as an add-on treatment for patients with SEA. It is also approved as an add-on treatment for paediatric use in SEA from ages six to 17 in Europe, the US and several other markets. In the US, Japan, Canada and a number of other markets, it is approved for use in adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). It was approved for use in patients 12 years and older with HES for ≥ six months without an identifiable non-haematologic secondary cause in the US in September 2020. Mepolizumab is currently being investigated in COPD. It is not currently approved for use in chronic rhinosinusitis with nasal polyps (CRSwNP) or COPD anywhere in the world.  

Important safety information

The following Important Safety Information is based on a summary of the European Summary of Product Characteristics and Prescribing Information for Nucala. Please consult the full Summary of Product Characteristics and Prescribing Information for all the safety information.

Nucala is contraindicated in patients with hypersensitivity to mepolizumab or to any of the excipients. Nucala should not be used to treat acute asthma exacerbations.

Asthma-related adverse symptoms or exacerbations may occur during treatment. Patients should be instructed to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment.

Abrupt discontinuation of corticosteroids after initiation of Nucala therapy is not recommended. Reduction in corticosteroid doses, if required, should be gradual and performed under the supervision of a physician.

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 have a delayed onset (i.e., typically within several 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 should be treated for the helminth infection before starting therapy with Nucala. If patients become infected whilst receiving treatment with Nucala and do not respond to anti-helminth treatment, temporary discontinuation of therapy should be considered.

In clinical studies in subjects with severe refractory eosinophilic asthma, the most commonly reported adverse reactions during treatment were headache, injection site reactions and back pain.  Headache was considered very common, occurring with a frequency of ≥1/10. Common adverse drug reactions (≥1/100 to <1/10) 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, non-allergic), local injection site reactions, and pyrexia. Severe allergic reactions (anaphylaxis) is a rare side effect (may affect up to 1 in 1,000 people).

Injection site reactions (e.g., pain, erythema, swelling, itching, and burning sensation) occurred at a rate of 8% in subjects treated with Nucala compared with 3% in subjects treated with placebo.

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.  

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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 under Item 3.D "Risk Factors" in the company's Annual Report on Form 20-F for 2019 and as set out in GSK’s “Principal risks and uncertainties” section of the Q3 Results and any impacts of the COVID-19 pandemic.