GlaxoSmithKline plc has announced the publication of results from a long-term open-label safety and efficacy study of Nucala (mepolizumab), a biologic treatment for patients with a form of asthma, known as severe eosinophilic asthma.
The study showed that treatment with mepolizumab had a safety profile similar to previous placebo-controlled studies, when patients received injections of mepolizumab for an average of 3.5 years and a maximum of 4.5 years. The study also showed that patients with severe eosinophilic asthma, who were treated with mepolizumab, had significant reductions in asthma attacks, known as exacerbations, and improvements in the control of their asthma symptoms.
Results published last week in The Journal of Allergy and Clinical Immunology (JACI) also showed that one third of patients in the study treated with mepolizumab experienced no asthma attacks, despite entering the study with an average of almost two attacks (1.74) per year.
Debbie Hartman, Respiratory Nurse Specialist at Hywel dda University health board in Glangwili Hospital in Wales said: “People with severe asthma are likely to experience frequent asthma attacks. Preventing these attacks is a priority for treating these patients to help improve their quality of life. Making sure patients whose symptoms remain uncontrolled on inhaled or oral therapy get the right add-on treatment can really transform their lives”.
Severe eosinophilic asthma is a type of asthma which can involve a patient’s symptoms remaining uncontrolled despite high-dose standard of care treatment. This specific form of asthma is driven by inflammation to the lungs caused by higher-than-normal levels of eosinophils (a type of white blood cell) being present in the blood, which can limit breathing and increase the frequency of asthma attacks. At normal levels, eosinophils can play a role in protecting the body against infection, but over-production can cause inflammation in vital organs and tissues, including the lungs, sometimes permanently damaging them.
Estimates suggest that there are 250,000 people in the UK who have severe asthma. Patients with severe eosinophilic asthma are typically unable to control their asthma symptoms despite taking combinations of many different high dose medications, including oral corticosteroids, and continue to suffer asthma attacks, which may require hospitalisation or an emergency room visit. Nucala is the first in class injectable biologic therapy licenced to treat these patients. It is an anti-IL-5 and works by preventing the ‘IL-5’ protein from binding to its receptor on the surface of the eosinophil cells, which in turn reduces eosinophil levels.
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 earlier 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 four weeks in addition to standard care for an average of 3.5 years (maximum 4.5 years on mepolizumab treatment).
- One third of patients (33%) treated with Nucala had no exacerbations despite entering the study with an average rate of almost two exacerbations a year (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, 0.80, year two, 0.82, year three, 0.71, year four, 0.80)
- Improvement in asthma control (improved (ACQ-5) 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), 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. On-treatment adverse events (AEs) were reported in 94% of patients. The most frequently reported on-treatment AEs were respiratory tract infection, headache, bronchitis, and asthma worsening. Seventy-nine (23%) patients experienced at least one on-treatment serious AE; there were six deaths, none assessed as related to mepolizumab.
- 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.
Due to the long-term nature of the study and natural attrition of subjects in studies of this duration, there were fewer patients (347 patients) in the later stages of the study than in the first two to three years.