AstraZeneca's tozorakimab add-on lowers exacerbation rate in COPD patients with prior exacerbations
核心洞察
Subcutaneous tozorakimab 300 mg every 4 weeks significantly lowered annualized moderate/severe COPD (搜索) exacerbation rates versus placebo in the replicate phase 3 OBERON and TITANIA trials.
Benefit was consistent in former smokers and across blood eosinophil thresholds, including patients with baseline eosinophils below 150 cells per microliter.
AstraZeneca said the anti-IL-33 (搜索) monoclonal antibody has FDA priority review, with a Prescription Drug User Fee Act date expected in the first quarter of 2027.
Add-on subcutaneous tozorakimab reduced annualized moderate/severe exacerbations versus placebo in adults with COPD (搜索) and a history of exacerbations, according to phase 3 results published in The New England Journal of Medicine and presented at the European Respiratory Society International Congress. The randomized, double-blind, placebo-controlled OBERON and TITANIA trials evaluated 300 mg tozorakimab every 4 weeks against placebo at week 52 in current or former smokers receiving stable inhaled maintenance therapy.
In OBERON, 877 patients were enrolled (mean age 67.1 years; 65.8% men; 91% on triple inhaled maintenance therapy), with 446 assigned tozorakimab and 431 to placebo. TITANIA enrolled 873 patients (mean age 68 years; 68.1% men; 90% on triple therapy), with 438 receiving tozorakimab and 435 placebo. Among former smokers, the annualized moderate/severe exacerbation rate was 1.34 versus 1.9 events in OBERON (rate ratio 0.71; 95% CI, 0.57-0.88) and 1.37 versus 2.07 events in TITANIA (RR 0.66; 95% CI, 0.55-0.8). Including current and former smokers, rates were 1.41 versus 2 events in OBERON (RR 0.7; 95% CI, 0.58-0.85) and 1.44 versus 2.03 events in TITANIA (RR 0.71; 95% CI, 0.59-0.84).
In the pooled population, lower rate ratios with tozorakimab were reported across subgroups defined by smoking status, age, sex, race and ethnic group categories, geographic region, prior exacerbation count, airflow obstruction severity, COPD (搜索) Assessment Test score, previous maintenance inhaled therapy, BMI and screening blood eosinophil count. The lowest rate ratio occurred in patients with eosinophils of 300 cells/µL or higher (RR 0.57; 95% CI, 0.44-0.74), followed by 150 to less than 300 cells/µL (RR 0.75; 95% CI, 0.6-0.92) and less than 150 cells/µL (RR 0.77; 95% CI, 0.62-0.94). Adverse event rates were comparable between arms in both trials, with injection site reactions reported more often with tozorakimab (OBERON 6.5% vs 3.3%; TITANIA 9.8% vs 4.6%). AstraZeneca said the FDA granted priority review and anticipates a Prescription Drug User Fee Act date in the first quarter of 2027.