On September 8, at the European Respiratory Society (ERS) Congress in Barcelona, AstraZeneca presented full results from its Phase III OBERON (NCT05166889) and TITANIA (NCT05158387) trials of its interleukin-33 (IL-33) inhibitor, tozorakimab, with simultaneous publication in the New England Journal of Medicine. The focus of this latest data presentation was the drug’s efficacy in reducing moderate and severe exacerbations among patients with chronic obstructive pulmonary disease (COPD) who continued to experience exacerbations despite inhaled standard-of-care therapy. The drug reportedly met primary and secondary endpoints across replicate trials, positioning it as potentially the first biologic to gain approval for a broad COPD population across all its severities.
OBERON and TITANIA were double-blind, placebo-controlled Phase III trials enrolling just over 2,300 patients with a history of two or more moderate or one or more severe COPD exacerbations in the prior 12 months; patients received either tozorakimab 300mg or placebo every four weeks for 52 weeks, layered on top of existing inhaled maintenance therapy.
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Inclusion criteria included both current and former smoking patients across all blood eosinophil counts (BEC) and all stages of lung function severity. The inclusion criteria were deliberately wide in order to test the drug beyond the eosinophil-high subgroups that have defined biologic success in COPD to date.
The drug reduced exacerbation rates in former smokers by 29% in the OBERON trial and by 34% in the TITANIA trial compared to placebo. Furthermore, perhaps the more consequential finding was the subgroup analysis by BEC: patients below 150 cells/µL, a population where most biologics in COPD have historically underperformed, saw a 23% reduction, rising to 34% at 150 or above and to 43% at 300 and above in both current and former smoking patients across both trials. According to the trials’ chief investigator, this marks the first time a COPD biologic has shown efficacy across the eosinophil spectrum, including below the 150 thresholds, regardless of smoking status.
Safety data suggested that the drug was generally well tolerated across both clinical trials, with severe adverse events leading to treatment discontinuation occurring in 3.1% and 3.7% in the OBERON and TITANIA trials, respectively.
Commercially, the data arrives alongside news that the FDA has accepted tozorakimab’s biologics licence application under a Priority Review Voucher, with a PDUFA date expected in Q1 2027, while regulatory review is also underway in the EU and China. This puts tozorakimab on a faster track than many rival IL-33s such as Roche’s astegolimab (Phase III ARNASA; NCT05595642) and gives AstraZeneca a strong new entry into a COPD biologics market that is still dominated by Dupixent (dupilumab), which works through the narrower IL-4/IL-13 axis, treating uncontrolled COPD patients with a type-2 inflammation (BEC of 300 cells/µL or more).
Sanofi’s market dominance in the respiratory space is expected to be tested, as AstraZeneca’s tozorakimab will compete directly against Dupixent across all severities of COPD, notwithstanding smoking status. Sanofi’s own IL-33 inhibitor, itepekimab, failed to achieve its primary endpoint in its Phase III AERIFY-2 trial (NCT04751487), leaving tozorakimab, for now, as the only IL-33 asset with positive Phase III data across the eosinophil spectrum. Nevertheless, Sanofi is not without countermeasures: it has ongoing trials evaluating its novel bispecific nanobody, lunsekimig, which targets thymic stromal lymphopoietin (TSLP) and IL-13, where it reported strong results from its Phase IIb (NCT06102005) in asthma at ERS 2026 and pending results from its Phase IIb/III (NCT07190209) for COPD. Sanofi therefore retains meaningful room to defend its position, even if AstraZeneca establishes an early lead in the broader COPD population.
GSK’s entry into the COPD biologics space in 2025 with its IL-5-targeting drug Nucala (mepolizumab), approved by the FDA in Q2 2025 and the EMA in Q1 2026, is also expected to intensify competition in the market. However, like Dupixent, Nucala is indicated only for moderate-to-severe COPD, highlighting the groundbreaking broad efficacy of tozorakimab.
Taken together, the OBERON and TITANIA results represent a breakthrough point for biologic treatment of COPD. By demonstrating clinically meaningful benefit across the eosinophil spectrum, including traditionally hard-to-treat, low-eosinophil and current-smoker populations, tozorakimab challenges the assumption that COPD biologics must be eosinophil-restricted to be effective. Combined with its favourable tolerability profile and Priority Review status, the drug is well positioned to become the first biologic approved for a broad COPD population, rather than the narrower severe segment served by Dupixent today. Still, with Sanofi advancing on its clinical trials for lunsekimig currently in Phase IIb/III for COPD, with its novel mechanism of action, this is expected to improve the company’s competitiveness in this space. And considering Nucala’s recent approval, tozorakimab’s ultimate commercial and clinical impact in COPD will depend on how convincingly these Phase III results translate into regulatory approval, physician adoption, and durable outcomes beyond the 52-week trial window. GlobalData’s COPD Market Drug Forecast expects the COPD market to grow to over $30bn across the seven major markets (US, France, Germany, Spain, Italy, UK, and Japan) by 2034, with Dupixent, Nucala, and tozorakimab as the leading players in that space.
