AstraZeneca on Tuesday released full results from two successful late-stage trials on its experimental drug for chronic obstructive pulmonary disease, boosting hopes that it could generate multibillion-dollar sales for the company.
The biologic medicine, tozorakimab, is under priority review by the Food and Drug Administration, with U.S. approval expected in the first quarter of 2027. The drug, administered once every four weeks, helped reduce flare-ups in a broad range of people with the condition.
“We truly believe that a large population of COPD patients can benefit from this new medicine,” Ruud Dobber, president of AstraZeneca’s biopharmaceuticals business unit, said in an interview.
The treatment reduced moderate and severe COPD flare-ups in the primary population of former smokers by 29% and 34%, respectively, compared to a placebo on top of the current inhaled standard of care. The drug, tozorakimab, also reduced moderate and severe flare-ups in a larger overall population of current and former smokers by 30% and 29%, respectively, compared to the placebo group.
The detailed data reinforces hopes that the product could be a breakthrough treatment for COPD, a progressive lung disease that blocks airflow and makes breathing difficult. An estimated 16 million to 26 million Americans, both diagnosed and undiagnosed, have COPD, and the condition is the fifth-leading cause of death in the U.S., according to AstraZeneca.
AstraZeneca recently raised its peak annual sales forecast for the drug to more than $5 billion, which could help the company reach its overall $80 billion revenue target by 2030. In an interview with CNBC, CEO Pascal Soriot said the drug has the opportunity to capture a broad group of patients.
“We believe it can be more than 5 billion, simply because the unmet need is huge,” Soriot said. “Patients are underdiagnosed; they need to be better diagnosed, and biologics in this class are totally underused. Maybe 10% of patients receive a biologic. Asthma is 30 to 40% depending on the country. So you can imagine the growth potential is very, very large.”
That optimistic outlook for the drug is driven by the fact that it could reach more patients than the currently available biologics for COPD – Dupixent and Nucala – which are limited to those with high levels of white blood cells called eosinophils.
Regeneron and Sanofi‘s Dupixent is one of the world’s top-selling medications, and GSK’s Nucala joined the COPD market last year.
“There’s still a huge number of patients who are not candidates for biologics with the current two approved drugs,” said Dr. Meilan Han, chief of the division of pulmonary and critical care at the University of Michigan Health and one of the investigators of the study.
Dobber added that AstraZeneca’s drug could “really change the treatment paradigm because of its broad utility.”
AstraZeneca’s two trials on tozorakimab included both former and current smokers, and patients across all blood eosinophil counts and all stages of lung function severity.
There is currently no biologic COPD medicine available for patients with a blood eosinophil count of below 150, said Dobber. Major clinical guidelines say that patients with lower eosinophil counts, especially under 100 to 150, generally indicate a low likelihood of responding to inhaled therapies.
In an analysis, the drug reduced moderate and severe flare-ups by 23% in that subset of patients, 34% in people with a blood eosinophil count at or above 150 and 43% in those at or above 300.
AstraZeneca’s drug works by blocking a protein called IL-33 that drives inflammation and mucus production, two of the underlying disease drivers of COPD. Several companies have pursued IL-33 treatments with limited success, leading some investors and researchers to question its potential.
“Tozorakimab is a product nobody thought would work. We ourselves had a very low probability of success,” Soriot said on the company’s second-quarter earnings call. ” … Everybody thought it would fail. If you look at the consensus before we announced the results, the consensus had almost zero in its forecast, and it actually worked.”
But the company believes its medicine succeeds where previous IL-33 drugs fell short because it targets the inflammatory protein in a different way. While earlier approaches largely focused on blocking one pathway linked to inflammation, AstraZeneca says its antibody is designed to inhibit two distinct IL-33 pathways, potentially addressing not only inflammation but also mucus production and airway damage that contribute to COPD.
AstraZeneca believes that broader approach may explain why the drug reduced exacerbations of the disease in a wide range of patients after years of setbacks for similar medicines.
From the prescriber perspective, Han said she will likely start patients with low eosinophil levels on the company’s drug.
But she said questions remain about where to use AstraZeneca’s drug relative to existing biologics for COPD patients with high eosinophil levels. She said because no head-to-head studies have compared AstraZeneca’s treatment to other biologics, doctors will likely still be evaluating whether the product should be used before or after currently available therapies in those patients after it enters the market.
She said she wants to see additional subgroup analyses to help make those decisions.
“I’m very excited about the data, but I am pushing them that I would like to see additional subgroup cuts of the data to understand how my patients might most benefit, so I can make the most informed decision possible,” she said. “I think it is a huge open question right now, both how providers are going to handle it, as well as how the GOLD committee will ultimately handle it.”
Han was referring to the Global Initiative for Chronic Obstructive Lung Disease Science Committee, which develops and updates international guidelines for diagnosing, managing and preventing COPD.
Dobber said the drug is currently under regulatory review for the treatment of COPD in major markets, including the EU and China. It is also being studied in a Phase 2 trial in severe asthma and Phase 3 study in severe viral lower respiratory tract disease.
“I truly believe that this can become one of the largest products in history in respiratory” for AstraZeneca, he said.
Dobber also pointed to growing concerns about air pollution and wildfire smoke as factors that can damage the lungs and increase the risk of COPD and disease flare-ups. While smoking remains a leading cause of the disease, he said environmental exposures are an important trigger that is often overlooked.
“Not everyone has a smoking history,” Dobber said, noting that tiny particles from sources such as wildfire smoke can irritate the lungs, which he called a “very sensitive organ.”
He said he hopes the attention around the new data will help raise awareness of COPD as a serious disease and spur broader efforts to reduce the factors that contribute to it.
