Nucala significantly reduces exacerbations in first global prospective real-world study of a biologic in severe eosinophilic asthma

Issued: London, UK

GlaxoSmithKline plc (GSK) today presented new data for Nucala (mepolizumab) from an interim analysis of REALITI-A, the first prospective global real-world study of a biologic treatment in patients with severe eosinophilic asthma. Results show a significant reduction in exacerbations and oral corticosteroid (OCS) use in patients after one year of treatment with Nucala when taken in a routine care setting, compared to the prior 12 months.

Christopher Corsico, Senior Vice President Development, GSK, said: “Exacerbations can be devastating for people living with severe eosinophilic asthma. The interim results from REALITI-A continue to demonstrate Nucala effectively reduces exacerbations, this time in a routine care setting. We look forward to sharing the full results from this study after it completes in 2021.”

REALITI-A is a two year, global, prospective, single-arm, observational study of patients with severe eosinophilic asthma newly prescribed Nucala and is being conducted in a routine care setting. The interim analysis of 368 patients presented at the 2019 European Respiratory Society (ERS) International Congress showed that, compared to the prior 12 months, after a year of treatment there was a:

• 69% reduction in the annual rate of clinically significant exacerbations (RR 0.31; 95% CI 0.27, 0.35), the primary endpoint of the study.
• 77% reduction in the annual rate of exacerbations requiring hospitalisation/emergency room visits (RR 0.23; 95% CI 0.18, 0.30).
• Reduction in median OCS dose (n=159) from 10 mg/day to 5mg/day, with 34% of patients (49/143) able to stop OCS completely.

Study investigator, Professor Tim Harrison, University of Nottingham and Nottingham University Hospitals NHS Trust, UK added: “Real-world studies like REALITI-A enhance our understanding of the beneficial effects medicines can make over and above data from randomised controlled trials. REALITI-A included a wider range of patients with severe asthma, studied in a setting that more closely resembles their everyday lives. Severe eosinophilic asthma can have a devastating impact on patients’ quality of life, so to see the interim analysis show patients benefitting from treatment with mepolizumab after a year is encouraging and mirrors my personal experience with using mepolizumab. I look forward to seeing the full results.”

Safety data from the study were consistent with results from previous clinical trials. 14% (53/368) of patients had on-treatment adverse events, with the most common being headache (23/368), nausea (5/368), fatigue (4/368), influenza like illness (4/368), back pain (3/368) and myalgia (3/368) and <1% (2/368) had on-treatment serious adverse events. There were no deaths.

REALITI-A is expected to complete in 2021 and full results will be published and presented at future scientific meetings in due course.

About real-world studies

Evidence demonstrating the efficacy and safety of medicines to support their regulatory approval is typically generated through randomised controlled trials (RCTs) which are considered the ‘gold standard’ of evidence-based medicine because of the highly rigorous controlled and scientific way in which they are conducted.

Real world data are data on patient health or healthcare delivery collected outside of a conventional RCT setting that reflect the everyday patient experience. Real world evidence is evidence derived from these data through the application of scientific research methods. Real world studies are not a replacement for RCTs, as they may not be able to account for certain biases or confounding factors the way an RCT can, however they can complement RCTs, providing information on a medicine’s effectiveness and safety in a routine care setting.

About REALITI-A

The REALITI-A (REAL world effectiveness of mepolizumab In paTIent care – Asthma) is a two year, global, prospective, single-arm, observational cohort study enrolling patients with severe eosinophilic asthma and newly prescribed mepolizumab 100mg subcutaneously at physician’s discretion (i.e. with no pre-defined eligibility criteria).

This is the first prospective global real-world study investigating a biologic in severe eosinophilic asthma and aims to recruit 850 patients across seven countries. Data are being collected at routine healthcare visits; one-year pre-exposure data are collected retrospectively at enrolment. The primary endpoint is the rate of clinically significant exacerbations (defined as exacerbations requiring oral corticosteroid use and/or emergency room visit/hospitalisation). Exacerbations requiring emergency room visit/hospitalisation and maintenance oral corticosteroid use are key secondary endpoints. The interim analysis presented at ERS includes patients with one-year post-exposure data. The study is expected to complete in 2021.

About severe asthma and eosinophilic inflammation  

Severe asthma is defined as asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy. Severe asthma patients are also often categorised by long-term use of oral corticosteroids (OCS). In a sub-set of severe asthma patients, the over-production of eosinophils (a type of white blood cell) is known to cause inflammation in the lungs. Interleukin-5 (IL-5) is the main promoter of eosinophil growth, activation and survival and provides an essential signal for the movement of eosinophils from the bone marrow into the lung. Studies suggest that approximately 60% of patients with severe asthma have eosinophilic airway inflammation.

About Nucala (mepolizumab)

First approved in 2015 for severe eosinophilic asthma, 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 without completely depleting them.

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 21 clinical trials across a number of eosinophilic indications and is the only biologic with 4.8 years of safety and efficacy data in severe eosinophilic asthma (SEA). Mepolizumab is approved (under the brand name Nucala) in the US, Europe and in over 20 other markets, as an add-on maintenance treatment for patients with SEA. It was approved for self-administration by patients aged over 12 in the US and EU in 2019. Mepolizumab is the only anti-IL5 biologic therapy approved for use in asthma patients aged six to 17 years in Europe and the US in SEA. In the US, Japan and Canada and a number of other markets, it is approved as add-on maintenance treatment for patients with eosinophilic granulomatosis with polyangiitis (EGPA). Mepolizumab is currently being investigated for severe hypereosinophilic syndrome, nasal polyposis and chronic obstructive pulmonary disease (COPD).

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 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.

Important safety information for Nucala (mepolizumab)

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.

GSK’s commitment to respiratory disease

For 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.

About GSK 

GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information, please visit www.gsk.com/about-us.

Trademarks are owned by or licensed to the GSK group of companies.

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 2018.