Nucala (mepolizumab) study reports long-term safety data, consistent exacerbation reduction and improved asthma control

GlaxoSmithKline plc (GSK) today presented new data from the longest study of an anti-IL5 biologic treatment in severe eosinophilic asthma to be reported. The study showed consistent reductions in exacerbations and improvements in asthma control, with a safety profile similar to previous clinical studies, in severe eosinophilic asthma patients treated with Nucala (mepolizumab) over the long-term study period. One third of patients in the study treated with mepolizumab experienced no exacerbations, despite entering the study with an average of almost two exacerbations (1.74) per year.

The open-label COLUMBA study, presented at the American Thoracic Society (ATS) conference, is a long-term safety and efficacy study of mepolizumab in patients with severe eosinophilic asthma. The study reports data from patients who were on mepolizumab treatment for an average of 3.5 years and a maximum of 4.5 years. Results showed:

• 61% decrease in exacerbation rate (from 1.74 events/year at enrolment to 0.68 events/year during the treatment period; 95% confidence interval 0.60, 0.78)
• Consistent exacerbation rates per year over the study period (year one, 0.71, year two, 0.82, year three, 0.71)
• Improvement in asthma control (improved (ACQ5) by -0.47) from first assessment (Week 12) and maintained for over four years (until Week 228).
• 78% reduction in blood eosinophils (white blood cells that cause inflammation in certain people with severe asthma), by week 4, sustained until the end of the study.
• Safety and immunogenicity profiles of long-term Nucala treatment observed in the COLUMBA study similar to that seen in prior severe asthma studies
• Initial improvements in lung function (mean pre-bronchodilator FEV₁) gradually decreased over the study period, reflecting the general decline in lung function expected in this patient population

Dave Allen Head, Respiratory Therapy Area R&D, GSK said: “These new data give us evidence that Nucala, a targeted biologic treatment, provides an enduring benefit to patients with severe eosinophilic asthma. The findings show the sustained exacerbation reduction and asthma control delivered by this medicine over a substantial length of time, with no new safety findings.”  

Sumita Khatri, Associate Professor of Medicine at Cleveland Clinic, Ohio and Principal Investigator in the COLUMBA study said: “People with severe eosinophilic asthma for whom control has not been possible with inhaled or oral therapy have always sought options to improve control. We know this may be achieved with biologic therapy and are excited to see the long-term effectiveness of the anti-IL-5 therapy, Nucala, balanced with a long-term safety profile.”

About the COLUMBA study

COLUMBA was a long-term, open-label extension study, which investigated the efficacy and safety of mepolizumab in patients with severe eosinophilic asthma who participated in the 12-month DREAM study. In the COLUMBA study 347 patients, who had been out of the DREAM study for at least 12 months, received 100 mg subcutaneous mepolizumab every 4 weeks in addition to standard care for an average of 3.5 years (maximum 4.5 years on mepolizumab treatment).  

Due to the long-term nature of the study and natural attrition of subjects in studies of this duration, there were fewer patients in the later stages of the study than in the first two to three years.                          

About Nucala (mepolizumab)

Nucala (mepolizumab) is the first-in-class biologic treatment for patients with severe eosinophilic asthma.  It is approved in over 40 countries including the EU, US, and Japan and has been prescribed to over 18,000 patients in the US.   It has been studied in over 3,000 patients in 16 clinical trials across a number of eosinophilic conditions.  Nucala (300mg) was recently approved in the US for the treatment of adult patients with a rare disease called eosinophilic granulomatosis with polyangiitis (EGPA). A sBLA has also been filed for the treatment in patients with chronic obstructive pulmonary disease and is currently being investigated for severe hypereosinophilic syndrome and nasal polyposis.

When inflammation occurs in the lungs it can affect the airways, making breathing difficult and increasing the frequency of exacerbations or asthma attacks. Although the mechanism of action has not been definitively established, Nucala is believed to work by preventing the ‘IL-5’ cytokine from binding to its receptor on the surface of the eosinophil cells, which in turn reduces eosinophil levels.

About severe eosinophilic asthma

Severe eosinophilic asthma is driven by inflammation linked to higher-than-normal eosinophils (a type of white blood cell) being present in the blood. When present in the body in normal levels, eosinophils can play a role in protecting the body against infection but over-production can cause inflammation in vital organs and tissues, sometimes permanently damaging them.

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

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 (3x 100mg subcutaneous injection of mepolizumab) is licensed for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). Nucala is not approved for the 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: www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003860/WC500198037.pdf

GSK’s commitment to respiratory disease

GSK has led the way in developing innovative medicines to advance the management of asthma and COPD for nearly 50 years. Over the last five years we have launched six innovative medicines responding to continued unmet patient need, despite existing therapies. This is an industry leading portfolio in breadth, depth and innovation, developed to reach the right patients, with the right treatment.

We remain at the cutting-edge of scientific research into respiratory medicine, working in collaboration with patients and the scientific community to offer innovative medicines aimed at helping to treat patients’ symptoms and reduce the risk of their disease worsening. While respiratory diseases are clinically distinct, there are important pathophysiological features that span them, and our ambition is to have the most comprehensive portfolio of medicines to address a diverse range of respiratory diseases. To achieve this, we are focusing on targeting the underlying disease-driving biological processes to develop medicines with applicability across multiple respiratory diseases. This approach requires extensive bioinformatics, data analytic capabilities, careful patient selection and stratification by phenotype in our clinical trials.

Important Safety Information for Nucala

The following information is based on 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 (e.g. anaphylaxis, 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, 3% of subjects who received Nucala experienced systemic (allergic and nonallergic) reactions compared to 5% 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. Reports of anaphylaxis have been received postmarketing.

Injection site reactions (e.g. pain, erythema, swelling, itching, 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

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.

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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 Principal risks and uncertainties in the company's Annual Report on Form 20-F for 2017.