GSK Submits NUCALA for COPD Indications

Mepolizumab (NUCALA), an investigational therapy for chronic obstructive pulmonary disease (COPD), will now be considered by the US Food and Drug Administration (FDA) for COPD patients with an eosinophilic phenotype.

GlaxoSmithKline (GSK) announced a supplemental Biologics License Application (sBLA) for the therapy Wednesday, featuring data from the phase 3 METREX and METREO studies.

The interleukin-5 (IL-5) antagonist, which is being investigated for its utility as an add-on maintenance therapy for certain COPD patients, is currently not approved for COPD anywhere in the world.

A week prior to the announcement, GSK shared guidelines for NUCALA patient prescription at the 2017 Annual CHEST Meeting in Toronto, ON, CA. Jean-Pierre Llanos, MD, GSK’s US Medical Affairs Lead for the therapy, explained that NUCALA is indicated for patients aged 12 years and older with severe asthma with an eosinophilic phenotype.

Though it affects anywhere between 5% and 10% of the asthma population, severe asthma has a history of varied criteria, used inconsistently, to define it, Llanos said.

“It’s very important you identify exactly which patient will benefit from the biologic — in this case, NUCALA,” Llanos said. “To remind you just what a severe asthmatic patient is, we’re using information from ERS/ATS 2014.”

The definition, as set in 2014 by the European Respiratory Society and American Thoracic Society, requires that patients have uncontrolled asthma despite a high-dose inhaled corticosteroid (ICS) plus a long-acting beta 2 agonist (LABA), or leukotriene modifier/theophylline for the previous year — or corticosteroids for at least half of the previous year.

Llanos recommended a dose of 100mg once every 4 weeks via subcutaneous injection, as administered by a healthcare professional. Because it is a biologic agent, he advised patient monitoring to the CHEST crowd.

NUCALA serves as a COPD therapy by inhibiting signaling of the IL-5 — the major cytokine behind eosinophil growth, differentiation, recruitment, activation, and survival.

“As we’ve seen in our trials, we get up to an 84% reduction in eosinophils,” Llanos said.

In 2 of 4 select phase 3 trials, Llanos showed NUCALA’s efficacy versus placebo in qualified COPD patients.

The first, the Dose-ranging and Exacerbation (DREAM) Study, randomized 616 patients 1:1:1:1 into intravenous treatment groups. Treatment groups included mepolizumab 750mg every 4 weeks; mepolizumab 250mg every 4 weeks; mepolizumab 75mg every 4 weeks; and placebo every 4 weeks.

With a primary endpoint of reduced annual rates of asthma exacerbations, the 75mg NUCALA population reported 1.24 exacerbations per year, versus the 2.4 per-year rate reported in the placebo population.

The Confirmatory Exacerbation (MENSA) Study reiterated those results, with 3 treatment groups randomized with 576 asthma patients who had at least 2 exacerbations while on particular therapy in the past year. Mepolizumab 75mg patients reported .83 exacerbations per year, versus placebo patients’ rate of 1.74 per year.

Including the results of the proceeding Quality of Life (MUSCA) Study, and Confirmatory OCS Reduction (SIRIUS) Study, NUCALA has been found to reduce exacerbations and oral corticosteroid doses, while maintain asthma control, Llanos said. It’s also been found to improve patient quality of life and their control over asthma.

GSK, which funded Llanos' CHEST presentation, said they intend to follow their US FDA application with regulatory filings to other countries in 2017 and 2018.

A press release regarding the application was made available.