GSK The FDA on May 22 cleared GSK’s interleukin-5 antibody Nucala (mepolizumab) as an add-on to inhaled triple therapy for adults whose chronic obstructive pulmonary disease keeps flaring despite treatment and whose blood-eosinophil count starts at 150 cells/µL.

The approval is on the basis of the MATINEE and METREX phase 3 trials.

The MATINEE study, which included 804 patients, found that Nucala reduced these exacerbations by 21% annually (rate ratio 0.79; 95% CI 0.66–0.94; P = 0.01). The earlier METREX trial, involving 836 patients, showed an 18% reduction in the same measure (rate ratio 0.82; 95% CI 0.68–0.98; P = 0.04).

The METREX trial, completed in 2017, showed an 18% reduction in moderate/severe exacerbations (rate ratio 0.82, p=0.04) in patients with eosinophilic phenotype.

In addition, data from the MATINEE study indicated a trend towards 35% fewer emergency room visits or hospitalizations for patients receiving Nucala.

A novel biologic for eosinophilic COPD

Nucala is now the first biologic cleared to tackle eosinophilic COPD, a population GSK pegs at more than 1 million U.S. patients whose disease keeps flaring despite the availability of “triple-combo” inhalers.

The FDA win comes years after an FDA advisory committee voted 16-3 against recommending mepolizumab as an add-on treatment for COPD in 2018. At that time, the adcomm noted that one of two pivotal trials (METREO) failed to meet endpoints while also citing a lack of patient history data that could have affected results and uncertainty about the definition of “eosinophilic COPD.” The resulting complete response letter called for more clinical data to support approval.

That led to MATINEE, a trial GSK intended to supplement METREX and METREO. MATINEE built on our learnings from these prior studies and IL-5 science to identify the patients who could benefit the most from the therapy. In sum, MATINEE had more rigorous patient selection criteria, requiring blood eosinophil count ≥300 cells/μL (vs. METREX’s broader criteria). It also had a longer study duration of up to 104 weeks vs. 52 weeks and refined endpoints, focusing on the most clinically relevant outcomes. In sum, MATINEE addressed all the advisory committee’s 2020 concerns.