By Will Boggs MD
NEW YORK (Reuters Health) - 24/5/2019
"Benralizumab had substantial reduction in peripheral blood eosinophils and, in a subset, sputum eosinophils, but did not reach the primary endpoint of exacerbation-rate reduction despite enrolling a patient population enriched for those with an increase in peripheral blood eosinophils and a past history of exacerbations," said Dr. Gerald J. Criner from Lewis Katz School of Medicine, Temple University, in Philadelphia.
"This suggests that these parameters do not identify a patient population that benefits from this therapy," he told Reuters Health by email.
In an earlier phase 2 trial, benralizumab reduced exacerbations in COPD patients with baseline eosinophil counts of 200/mm3 or greater, but not in the overall population of patients with COPD.
Dr. Criner and colleagues in the GALATHEA and TERRANOVA trials investigated the efficacy and safety of benralizumab for preventing exacerbations in patients with moderate to very severe COPD, aiming to enroll twice as many patients with eosinophil counts of 220/mm3 or more as with lower eosinophil accounts.
In both trials, the annualized COPD exacerbation rates did not differ significantly between the benralizumab and placebo groups, the researchers report in the New England Journal of Medicine, online May 20. The paper was published to coincide with a presentation at the American Thoracic Society annual meeting in Dallas, Texas.
Changes in pre-bronchodilator forced expiratory volume in one second (FEV1) and in St. George's Respiratory Questionnaire total scores did not differ between the groups. All benralizumab doses were followed by substantial depletion of blood eosinophils from week 4 to the end of the trial, but there was no eosinophil depletion after placebo administration.
Treatment effects did not differ between baseline eosinophil counts divided into categories ranging from <150/mm3 to >400/mm3.
"In post hoc analysis, patients with a history of >3 prior exacerbations or on triple inhaled therapy had greater effect on exacerbation reduction with treatment with 100 mg benralizumab, and a sensitivity analysis showed a >40% reduction in severe exacerbations that required hospitalization," Dr. Criner said. "Also, baseline eosinophil levels >300 cells were associated with a greater benralizumab effect in those treated with 100-mg doses. Future studies using these selection criteria may identify a patient group who may benefit from this therapy."
"Exacerbations are a common problem in patients with COPD, but with heterogeneous mechanisms involved, they will need individualized treatments," he said. "Targeted therapies like benralizumab are an important step forward, but more work is required to identify the patient population that will most benefit from this therapy."
AstraZeneca funded the trials and employed several of the authors.
N Engl J Med 2019