Tozorakimab Sustains COPD Exacerbation Benefit to 2 Years: Henrik Watz, MD

Tozorakimab, an investigational anti-interleukin-33 (IL-33) monoclonal antibody, sustained reductions in chronic obstructive pulmonary disease (COPD) exacerbations for up to 104 weeks in an integrated analysis of the phase 3 OBERON, TITANIA, and PROSPERO trials, although it narrowly missed its primary severe exacerbation endpoint in former smokers.1 Henrik Watz, MD, professor of clinical research in respiratory medicine at the University of Lübeck, medical director at Velocity Clinical Research in Ahrensburg, Germany, and COPD disease area coordinator for the German Center for Lung Research, presented the analysis at the CHEST 2026 Annual Meeting, held October 18-21, 2026, in Phoenix, Arizona, and discussed the findings with HCPLive.

PROSPERO (NCT05742802) enrolled patients completing OBERON (NCT05166889) or TITANIA (NCT05158387), which showed fewer moderate to severe exacerbations with add-on subcutaneous tozorakimab 300 mg every 4 weeks versus placebo.1,2 The integrated analysis included 884 patients receiving tozorakimab and 866 receiving placebo.

"So for me as a doctor treating patients with COPD hospitalizations on a daily basis, I know that these kind of events are the most life-changing and, in terms of prognosis, most relevant events, so the life is never the same in our patients after hospitalization for severe exacerbation as it was before," Watz said.

The annualized severe exacerbation rate in former smokers, the primary endpoint, was 0.26 with tozorakimab versus 0.33 with placebo (rate ratio [RR], 0.79; 95% CI, 0.61–1.01; P = .0587), so no further inferential testing was performed.1 In the overall population of current and former smokers, the rate was 0.26 versus 0.36 (RR, 0.73; 95% CI, 0.58–0.91; nominal P = .0046).

Nominal reductions were also seen overall for exacerbations resulting in a hospital visit (RR, 0.69; 95% CI, 0.57–0.85; P = .0003) and for moderate to severe exacerbations (1.43 vs 2.05 per year; RR, 0.70; 95% CI, 0.62–0.79; P < .0001).1 Adverse event incidence through 104 weeks was similar between groups (81.9% vs 82.0%), except for injection-site reactions.

Watz said tozorakimab, if approved, would serve as add-on maintenance therapy for patients with frequent exacerbations despite triple inhaled therapy, with blood eosinophil count carrying less weight in patient selection. These congress data have not been peer reviewed.

Relevant disclosures for Watz include AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, and Sanofi.

References

1. Watz H, Sciurba FC, Bourdin A, et al. Long-term efficacy and safety of tozorakimab in patients with COPD: an integrated analysis of OBERON, TITANIA and the PROSPERO extension study. Presented at: CHEST 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.

2. Long-term efficacy and safety of tozorakimab in participants with chronic obstructive pulmonary disease with a history of exacerbations (PROSPERO). ClinicalTrials.gov identifier: NCT05742802. Accessed October 20, 2026. https://clinicaltrials.gov/study/NCT05742802