GlaxoSmithKline : New data published for GSK’s Nucala investigating hospitalisation reduction in severe asthma patients with an eosinophilic phenotype

Issued: London

GlaxoSmithKline plc (GSK) today announced the publication of a meta-analysis in the Journal of Allergy and Clinical Immunology, which demonstrates that the risk of hospitalisations or emergency room visits caused by asthma attacks was halved (51% reduction p<0.001) in severe asthma patients with an eosinophilic phenotype who received Nucala (100mg fixed dose subcutaneous injection of mepolizumab) or an investigational dose of mepolizumab, compared to placebo and in addition to standard of care.

Steve Yancey, Medicines Development Lead for mepolizumab, GSK, and one of the study authors, said: 'We know that hospitalisations have a detrimental impact on asthma patients, their families and the healthcare system. Therefore, reducing the risk of an asthma attack, which is so severe it requires hospital intervention, is a crucial aspect of asthma management. These findings demonstrate the important role that targeted treatment using Nucala can play for severe asthma patients with an eosinophilic phenotype in addressing an aspect of asthma that is a major concern for patients.'

The meta-analysis looked at data from 1388 patients across four randomised placebo-controlled clinical trials ranging from 24 to 52 weeks in duration, including the pivotal phase III MENSA trial (MEA115588). All patients included in the meta-analysis had frequent exacerbations and were already receiving standard of care. This included high-dose inhaled steroids plus at least one additional controller medicine, which in most patients was a long-acting bronchodilator and in some cases maintenance oral corticosteroids. The results of the meta-analysis suggest mepolizumab provides an important clinical benefit in reducing major events such as hospitalisations and visits to the emergency room in severe asthma patients with an eosinophilic phenotype already on a background of appropriate standard therapy.

Severe asthma is a chronic condition that affects a small, but significant, number of patients who need to take multiple medications to control their day-to-day symptoms and to reduce the risk of frequent and serious asthma attacks. For some of these patients, their condition is driven by inflammation in the lungs caused by increased levels of eosinophils, a type of white blood cell. For patients whose severe asthma is driven by eosinophilic inflammation, treatment options have been limited.

Nearly 40% of severe asthma patients are hospitalised at least once a year for the treatment of an asthma attack. In addition to the impact on patients, asthma attacks are also associated with increased healthcare costs, with studies suggesting that costs are up to three or four times higher for severe asthma patients compared with mild asthma patients. Exacerbations (especially those resulting in hospitalisation) are one of the main reasons for high healthcare costs associated with severe asthma patients.

About Nucala

Nucala is the first-in-class anti-IL-5 biologic therapy. Nucala was specifically developed to treat appropriate severe asthma patients whose condition is driven by inflammation caused by eosinophils, a type of white blood cell. Nucala binds to IL-5, preventing it from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding in this way reduces blood, tissue and sputum eosinophil levels.

In the US, Nucala (100mg fixed dose subcutaneous injection of mepolizumab) is licensed as an add-on maintenance treatment for patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. Nucala is not approved for the treatment of other eosinophilic conditions or relief of acute bronchospasm or status asthmaticus. Full US Prescribing Information is available at US Prescribing Information Nucala.

In the EU, Nucala (100mg fixed dose subcutaneous injection of mepolizumab) is licensed as an add-on treatment for severe refractory eosinophilic asthma in adult patients. For the EU Summary of Product Characteristics for Nucala, please visit: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003860/WC500198037.pdf

Nucala has also been approved in Canada, Australia, Japan, Switzerland, Chile, South Korea and Taiwan. Further regulatory applications have been submitted and are under review in other countries.

Nucala is a registered trade mark of the GSK group of companies.

Important Safety Information for Nucala

The following information is based on the Highlights section of the US Prescribing Information for Nucala. Please consult the full Prescribing Information for all the labelled safety information for Nucala.

CONTRAINDICATIONS

Nucala should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions (eg, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred following administration of Nucala. These reactions generally occur within hours of administration but in some instances can have a delayed onset (i.e. days). In the event of a hypersensitivity reaction, Nucala should be discontinued.

Acute Asthma Symptoms or Deteriorating Disease

Nucala should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.

Opportunistic Infections: Herpes Zoster

In controlled clinical trials, 2 serious adverse reactions of herpes zoster occurred in subjects treated with Nucala compared to none in placebo. Consider varicella vaccination if medically appropriate prior to starting therapy with Nucala.

Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids (ICS) abruptly upon initiation of therapy with Nucala. Decreases in corticosteroid doses, if appropriate, should be gradual and under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection

It is unknown if Nucala will influence a patient's response against parasites. Treat patients with pre-existing helminth infections before initiating therapy with Nucala. If patients become infected while receiving treatment with Nucala and do not respond to anti-helminth treatment, discontinue treatment with Nucala until infection resolves.

ADVERSE REACTIONS

The most common adverse reactions (≥3% and more common than placebo) reported in the first 24 weeks of two clinical trials with Nucala (and placebo) were: headache, 19% (18%); injection site reaction, 8% (3%); back pain, 5% (4%); fatigue, 5% (4%); influenza, 3% (2%); urinary tract infection 3% (2%); abdominal pain upper, 3% (2%); pruritus, 3% (2%); eczema, 3% (<1%); and muscle spasm, 3% (<1%).

Systemic Reactions, including Hypersensitivity Reactions: In 3 clinical trials, 10% of subjects who received Nucala experienced systemic (allergic and nonallergic) and local site reactions compared to 7% in the placebo group. Systemic allergic/hypersensitivity reactions were reported by 1% of subjects who received Nucala compared to 2% of subjects in the placebo group. Manifestations included rash, pruritus, headache, and myalgia. Systemic nonallergic reactions were reported by 2% of subjects who received Nucala and 3% of subjects in the placebo group. Manifestations included rash, flushing, and myalgia. A majority of the systemic reactions were experienced on the day of dosing.

Injection Site Reactions: 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.

USE IN SPECIFIC POPULATIONS

A pregnancy exposure registry monitors pregnancy outcomes in women exposed to Nucala during pregnancy. Healthcare providers can enrol patients or encourage patients to enrol themselves by calling 1-877-311-8972 or visiting www.mothertobaby.org/asthma.

The data on pregnancy exposures from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as mepolizumab, are progressively transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential effects on a foetus are likely to be greater during the second and third trimesters of pregnancy.

GSK - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

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 2015.

1. Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma. Yancey S, Ortega H, Keene O, Mayer B, Gunsoy N, Brightling C, Bleecker ER, Haldar P, Pavord I. Journal of Allergy and Clinical Immunology, 2016. http://www.jacionline.org/article/S0091-6749(16)30891-0/fulltext