Can the new injection tozorakimab cut COPD flare-ups?
Yes. In two identical trials with 1,750 people with COPD, those given tozorakimab had about 1.4 moderate or severe flare-ups a year, compared with about 2.0 on placebo. That works out to about 59 fewer flare-ups for every 100 people treated for a year, a drop of about 30%.
COPD, or chronic obstructive pulmonary disease, is a long-term lung disease that makes it hard to breathe. Flare-ups, which doctors call exacerbations, are stretches when breathing suddenly gets worse. Many people with COPD keep having them even while using standard daily inhalers.
Tozorakimab is a lab-made antibody that blocks interleukin-33 (IL-33), a signaling protein in the immune system. Faulty IL-33 signaling is thought to play a part in how COPD develops. In these trials, people got a tozorakimab or placebo injection every four weeks on top of the inhalers they were already using.
What the data show
The two trials, called OBERON and TITANIA, were run the same way so that each could check the other. Across everyone enrolled, both trials landed in almost the same place. In OBERON, people on tozorakimab averaged 1.41 flare-ups a year versus 2.00 on placebo, about 30% fewer (rate ratio 0.70). The true drop is very likely somewhere between 15% and 42%. In TITANIA, the rates were 1.44 versus 2.03, about 29% fewer (rate ratio 0.71), very likely between 16% and 41%.
In both trials, that gap equals about 59 fewer flare-ups per 100 people per year. Each of these two whole-group results had less than a 1 in 1,000 chance of being a coincidence. The trials’ main test, though, looked at a narrower group.
Results in former smokers
The researchers chose former smokers as the group for their main test. In OBERON, former smokers on tozorakimab had 1.34 flare-ups a year versus 1.90 on placebo. That is about 56 fewer flare-ups per 100 people per year, or about 29% fewer (rate ratio 0.71), very likely between 12% and 43% fewer. A result this strong would show up by chance only about 2 times in 1,000 if the drug did nothing (P = 0.002).
In TITANIA, former smokers had 1.37 flare-ups a year on tozorakimab versus 2.07 on placebo. That is about 70 fewer per 100 people per year, or about 34% fewer (rate ratio 0.66), very likely between 20% and 45% fewer, with less than a 1 in 1,000 chance of coincidence.
Dr. Kumar’s Take
Two trials giving the same answer carry more weight than one. OBERON enrolled 877 people and TITANIA enrolled 873, and both showed roughly a 30% drop in flare-ups. That kind of repeat result is what separates a real effect from a lucky one.
The benefit is real but not dramatic. People on the drug still averaged about 1.4 flare-ups a year. Tozorakimab lowered the flare-up rate. It did not stop flare-ups.
The trials also had no entry rule based on blood eosinophil count. Eosinophils are a type of white blood cell tied to allergy-type inflammation. Because nobody was screened out on that test, the results come from a broad mix of people with COPD rather than one narrow blood profile.
How the trials were done
Both trials enrolled adults with COPD who were current or former smokers. Everyone had a history of flare-ups in the previous year even though they were on stable standard inhaler therapy. People were randomly assigned to tozorakimab 300 mg or a placebo, given as a shot under the skin every 4 weeks for 52 weeks. The main goal was the yearly flare-up rate among former smokers. The first key secondary goal was the same rate across everyone. The results were published in the New England Journal of Medicine.
Safety and limits
Adverse events, meaning any health problem during the trial whether or not the drug caused it, were not more common with tozorakimab. In OBERON, 70.4% of people on the drug had an adverse event, compared with 77.2% on placebo. In TITANIA, the figures were 80.1% and 79.8%.
Two limits matter. The trials ran for one year, so they cannot speak to safety over many years of use. They were also funded by AstraZeneca, and several of the authors work for the company. Independent studies over longer periods would make these results stronger.
Practical Takeaways
- If you have COPD and still get flare-ups on your usual inhalers, know that tozorakimab was tested as an add-on to those inhalers, not a replacement for them.
- Expect fewer flare-ups rather than none, since people on tozorakimab still averaged about 1.4 moderate or severe flare-ups a year in these trials.
- If flare-ups keep happening despite your current treatment, ask your lung doctor about add-on treatment options, because this study shows the flare-up rate can still be pushed down.
Related Studies and Research
- Long-term oxygen for COPD: the LOTT trial found no benefit
- Does oxygen help COPD patients train harder?
- High-flow oxygen during exercise training in COPD
- Semaglutide linked to 40% fewer asthma attacks in UK data
- How many people does second-hand smoke kill a year?
FAQs
What is tozorakimab?
Tozorakimab is a monoclonal antibody, a lab-made protein designed to lock onto one specific target in the body. Its target is interleukin-33, an immune signaling protein. By blocking IL-33, the drug aims to calm one of the signals thought to drive COPD. In these trials it was given as a 300 mg injection under the skin every four weeks. The OBERON and TITANIA trials were phase 3 studies, the large late-stage trials that test whether a drug works in a broad group of patients.
How is tozorakimab different from COPD inhalers?
Inhalers deliver medicine straight to the airways and are usually taken every day. Tozorakimab is injected under the skin once every four weeks and works through the immune system by blocking a single signal, IL-33. The two are not competitors. Every person in these trials stayed on their standard inhalers, and tozorakimab or placebo was added on top.
Does tozorakimab work for people who still smoke?
Current smokers were enrolled in both trials as part of the overall group. The overall results, which included current and former smokers together, showed about a 30% drop in flare-ups, almost the same as the result among former smokers alone. The main test was planned in former smokers, so that is where the evidence is strongest.
Bottom Line
In two identical phase 3 trials with 1,750 people with COPD who kept having flare-ups on standard inhalers, adding a tozorakimab injection every four weeks cut moderate or severe flare-ups by about 30% over a year. That meant about 1.4 flare-ups a year instead of about 2.0, or about 59 fewer flare-ups per 100 people treated for a year. Adverse events were no more common than on placebo. The trials lasted one year and were funded by AstraZeneca, but the matching results from two separate trials make this a strong early signal for a new way to treat COPD.
