Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations (OBERON and TITANIA)

doi:10.1056/nejmoa2606998

OBERON and TITANIA

Patient / Population Intervention / Exposition Vergleich Endpunkt

In 1,750 patients with COPD and exacerbations despite inhaled therapy, subcutaneous tozorakimab reduced moderate or severe exacerbations over 52 weeks compared with placebo.

N

1.750Patienten

Design

Two replicate phase 3, multicentre, randomised, double-blind, placebo-controlled trials (OBERON, NCT05166889; TITANIA, NCT05158387) in adults with symptomatic COPD, current or former smokers, with an exacerbation in the past year on stable inhaled maintenance therapy and no blood eosinophil entry criterion; add-on subcutaneous tozorakimab 300 mg or placebo every 4 weeks for 52 weeks. Both trials also randomised a tozorakimab regimen every 8 weeks, which the reported comparison leaves out

Endpunkt

Annualised rate of moderate or severe COPD exacerbations over 52 weeks in former smokers; the first key secondary is the same rate in the overall population of current and former smokers

Relevanz

1Praxisdefinierend — die Studie, auf der die Leitlinie ruht.

ErgebnisModerate or severe exacerbations among former smokers 1.34 vs 1.90 per year in OBERON (rate ratio 0.71, 95% CI 0.57-0.88; P = 0.002) and 1.37 vs 2.07 in TITANIA (rate ratio 0.66, 95% CI 0.55-0.80; P < 0.001). In the overall population of current and former smokers 1.41 vs 2.00 (rate ratio 0.70, 95% CI 0.58-0.85; P < 0.001) and 1.44 vs 2.03 (rate ratio 0.71, 95% CI 0.59-0.84; P < 0.001). Adverse events 70.4% vs 77.2% in OBERON and 80.1% vs 79.8% in TITANIA. The reported comparison covers 446 and 431 patients in OBERON and 438 and 435 in TITANIA, entered without any blood eosinophil threshold.

Sciurba FC, Watz H, Bourdin A, et al. Tozorakimab to Prevent COPD Exacerbations. N Engl J Med. 2026; published online 8 September. 10.1056/nejmoa2606998

Diskussion & Kritik

Two replicate phase 3 trials, both positive, and the first COPD biologic to work without selecting patients by blood eosinophils: entry asked for exacerbations on inhaled therapy and nothing else. A 30% cut in exacerbations puts tozorakimab where dupilumab sits on effect size, while opening the drug to the majority of patients an eosinophil threshold leaves out. The primary analysis was confined to former smokers and current smokers came in the first key secondary, a hierarchy built around a known dilution rather than a subgroup found afterwards, and both levels held in both trials. Safety was unremarkable, so the open question is durability and price rather than whether it works.