Long-Term Data Show One-Third of Patients Had No Exacerbations With Nucala Treatment

Patients with severe eosinophilic asthma who were treated with mepolizumab, sold by GlaxoSmithKline as Nucala, saw their rate of exacerbations drop significantly during a long-term study of the treatment, and a third had no exacerbations.

Data from the COLUMBA study were presented Sunday at the American Thoracic Society 2018 International Conference, being held in San Diego, California. COLUMBA followed 347 patients who had been taking the anti-IL5 biologic in an earlier study for 12 months, and followed them for an average of 3.5 years, with some followed as long as 4.5 years. The patients in COLUMBA received 100 mg of subcutaneous mepolizumab every 4 weeks in addition to standard care.

“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,” said Dave Allen, head of Respiratory Therapy Area Research and Development at GlaxoSmithKline, in a statement.

Eosinophilic asthma is a severe form of the condition that doesn’t respond well to inhaled corticosteroids, even at high doses. White blood cells called eosinophils become overactive, causing inflammation that blocks the airway with fluid and mucous. This can cause bronchial spasms. Unlike forms of asthma that are triggered by allergies or an environmental reaction, patients with this condition do not typically have a history of allergies.

Mepolizumab, a monoclonal antibody, targets interleukin-5, a type-1 cytokine that plays a key role in the triggering eosinophilic airway inflammation.

Results from COLUMBA showed:

• A 61% decline in the in exacerbation rate, from 1.74 events per year at enrollment to 0.68 events per year during the treatment period (95% confidence interval [CI] 0.60, 0.78).
• Exacerbation rates remained consistent from year to year during the study period (0.71 during year 1; 0.82, year 2; 0.71, year 3).
• There was a 78% reduction in eosinophils by week 4, which was sustained.
• Asthma control improved, as measured by the Asthma Control Questionnaire 5 (ACQ5). The rating improved 0.47 by week 12 and was sustained through the end of the study.

Frank Albers, MD, MD, PhD, Global Medical Lead, GlaxoSmithKline, Chapel Hill, North Carolina, explained that the patients taking part in COLUMBA were selected from those who had previously taken part in the DREAM study, but had stopped taking mepolizumab for between 12 and 28 months before enrolling in this second, long-term trial.

In an interview with The American Journal of Managed Care®, Albers explained that patients experienced a return of symptoms and exacerbations during the break from therapy, yet a third had no exacerbations once they were put back on the drug—a remarkable result for patients with a heavy symptom burden.

Results from COLUMBA answer many questions for physicians who treat patients with severe asthma, Albers said. “Because the anti-IL5 medicines are still relatively new on the market, it’s important for physicians to get an understanding of the long-term safety profile,” he said.

And because the study treated patients who had experienced a break in treatment, Albers explained, the results address real-world concerns. “The question we always hear from physicians is, ‘Is it possible to reintroduce the drug? Could I expect a loss of efficacy or any safety concerns?’ This study answers those questions well.”

GlaxoSmithKline has additional research under way to find out if some patients can stop treatment after an extended period, and if so, which ones. Asked whether long-term mepolizumab users might be given fewer doses, Albers said, “that is another question,” being considered.

The results also showed that there was an initial improvement in lung function that gradually eased over the study period, which researchers said reflects the overall decline in lung function seen in patients with severe asthma.

Common adverse reactions (which affected at least 3% of the participants and were more common than placebo) were headache, site reactions back pain, fatigue, influenza, urinary tract infection, abdominal pain, bursitis, eczema, and muscle spasms.

The abstract described adverse reactions “of special interest,” which included local injection site reactions (12%), opportunistic infections (7%), systemic reactions (3%), serious cardiac, vascular and thromboembolic events (3%), malignancies (2%), and serious ischemic events (<1%). Six patients died during the study.

GlaxoSmithKline funded the study.

Reference

Ortega H, Bradford ES, Albers FC, et al. Long-term safety of mepolizumab in patients with severe eosinophilic asthma: The COLUMBA Study. Presented at the American Thoracic Society 2018 International Conference; San Diego, California; May 18-23, 2018. Abstract A1367.