European Respiratory Society Congress 2026 | iPharmaCenter

AstraZeneca's Tozorakimab Becomes First Biologic to Cut COPD Flare-Ups Across All Patient Types

AstraZeneca has released complete data from two late-stage trials showing that its experimental antibody tozorakimab can meaningfully reduce the frequency of dangerous lung flare-ups in patients with chronic obstructive pulmonary disease, even among those who continue to suffer exacerbations despite using standard inhaled medications.

What the OBERON and TITANIA Trials Showed

The OBERON and TITANIA studies enrolled a combined 2,306 adults with symptomatic COPD who had experienced at least two moderate exacerbations or one severe exacerbation requiring hospitalization in the year before joining the trials. Patients received either tozorakimab 300 milligrams or placebo once every four weeks for 52 weeks, both on top of their existing inhaled maintenance therapy.

The trials were designed to test the drug in two populations. The primary group consisted of former smokers, while the broader population included both current and former smokers. This design matters because COPD affects both groups, and many previous treatments have shown weaker effects in patients who continue to smoke.

In former smokers, tozorakimab reduced the annual rate of moderate and severe exacerbations by 29 percent in OBERON and 34 percent in TITANIA compared with placebo. When looking at all patients regardless of smoking status, the reductions were 30 percent in OBERON and 29 percent in TITANIA. These figures represent the number of flare-ups patients experienced over the course of a year, not just whether they had any exacerbation at all.

Mucus Plugging: A New Endpoint

In a separate analysis presented at the ERS Congress, AstraZeneca researchers showed that tozorakimab reduced mucus plug scores in patients with COPD. Mucus plugs are accumulations of thick secretions that block airways and have been linked to worse lung function, more frequent exacerbations, and accelerated disease progression. The company states this is the first biologic to demonstrate a reduction in mucus plugging in a broad COPD population.

Tozorakimab - Mechanism of action

Tozorakimab targets interleukin-33, a signaling protein that sits near the top of multiple inflammatory cascades involved in COPD. By blocking both the reduced and oxidized forms of IL-33, the antibody aims to dampen inflammation while also interrupting the cycle of mucus overproduction and impaired clearance that contributes to airway obstruction.

Whether mucus plug reduction translates into long-term clinical benefits such as slower lung function decline or reduced mortality remains to be seen. But the finding adds biological plausibility to the exacerbation reduction data and suggests the drug may be affecting disease processes beyond just preventing acute flare-ups.

Regulatory Pathway

The FDA accepted AstraZeneca's Biologics License Application for tozorakimab as an add-on maintenance treatment for adult patients with COPD under Priority Review. The agency assigned a Prescription Drug User Fee Act target date in the first quarter of 2027, accelerated by the use of a Priority Review voucher. This timeline positions tozorakimab to potentially become the first IL-33 targeting therapy approved for COPD, and only the third or fourth biologic overall depending on the timing of other pipeline candidates.

Regulatory reviews are also underway in other major markets, including the European Union and China. AstraZeneca has not disclosed exact decision timelines for these regions, but European approval typically follows FDA approval by six to twelve months for novel mechanisms.

The Disease Burden

COPD affects hundreds of millions of people worldwide and causes more than 3 million deaths annually. In the United States alone, exacerbations trigger more than 2,500 emergency department visits every day. The condition is characterized by persistent airflow limitation, chronic airway inflammation, and symptoms including breathlessness, chronic cough, and excess mucus production.