AstraZeneca on Tuesday announced full results from two successful late-stage trials of its investigational drug for chronic obstructive pulmonary disease, raising hopes that it could generate billions of dollars in revenue for the company.
Tozolakimab, a biologic, is under priority review by the Food and Drug Administration, with U.S. approval expected in the first quarter of 2027. The drug, given once every four weeks, has helped reduce flare-ups in a wide range of people with the condition.
“We truly believe that many people with COPD will benefit from this new drug,” Ruud Dobber, president of AstraZeneca’s biopharmaceutical business, said in an interview.
This treatment reduced moderate and severe COPD flare-ups by 29% and 34%, respectively, in a key population of ex-smokers compared to current inhaled standard therapy plus a placebo. The drug also reduced moderate and severe relapses by 30% and 29%, respectively, across a larger population of current and former smokers compared to the placebo group.
Detailed data supports hopes that the product could be a breakthrough treatment for COPD, a progressive lung disease that blocks airflow and causes difficulty breathing. According to AstraZeneca, an estimated 16 million to 26 million Americans, both diagnosed and undiagnosed, have COPD, making the disease the fifth leading cause of death in the United States.
AstraZeneca recently raised its peak annual sales forecast for the drug to more than $5 billion, which could help the company reach its overall revenue goal of $80 billion by 2030. CEO Pascal Soriot said in an interview with CNBC that the drug has an opportunity to reach a broader group of patients.
“We think that number could be over $5 billion, just because the unmet need is so large,” Soriot said. “Patients are underdiagnosed, we need better diagnosis, and this class of biologics is not being used at all. Perhaps 10% of patients receive biologics. Asthma is 30% to 40%, depending on the country. So you can imagine the potential for growth is huge.”
Optimism for the drug comes from the fact that it may be able to reach more patients than the currently available biologics for COPD, Dupixent and Nucala, which are limited to patients with high levels of white blood cells called eosinophils.
regeneron and sanofiDupixent is one of the best-selling drugs in the world. G.S.K.■ Nucala entered the COPD market last year.
“There are still a huge number of patients who are not candidates for biologics of the two currently approved drugs,” said Dr. Meylan Han, chief of the Division of Respiratory and Critical Care Medicine at Michigan Health University and one of the study’s researchers.
Dobber added that AstraZeneca’s drug “has the potential to significantly change the treatment paradigm because of its wide range of uses.”
The two trials of AstraZeneca’s tozolakimab included both former and current smokers, and patients at all levels of blood eosinophil count and lung function severity.
Currently, there are no biological COPD drugs available for patients with blood eosinophil counts below 150, Dobber said. Major clinical guidelines state that patients with low eosinophil counts, particularly those below 100 to 150, indicate that they are generally less likely to respond to inhaled therapy.
According to the analysis, the drug reduced moderate and severe flare-ups by 23% in some patients, 34% in people with blood eosinophil counts of 150 or higher, and 43% in people with blood eosinophil counts of 300 or higher.
AstraZeneca’s drug works by blocking a protein called IL-33, which promotes inflammation and mucus production, two of the fundamental disease factors in COPD. Several companies have pursued IL-33 treatments, but with limited success, and some investors and researchers question its potential.
“Tozolakimab is a product that no one thought would work, and our own chances of success were very low,” Soriot said during the company’s second-quarter earnings call. “Everyone thought it was going to fail. If you look at the consensus before the earnings release, the consensus expectation was almost zero, but it actually worked out.”
But the company believes that because its drug targets inflammatory proteins in a different way, it will succeed where previous IL-33 drugs fell short. While previous approaches focused primarily on blocking one pathway associated with inflammation, AstraZeneca says its antibody is designed to inhibit two different IL-33 pathways and could potentially address not only inflammation but also mucus production and airway damage that contribute to COPD.
AstraZeneca believes a broader approach may explain why its drug has been able to reduce worsening of the disease in a wide range of patients, after years of setbacks with similar drugs.
From a prescriber’s perspective, Han said patients with low eosinophil levels would likely start receiving the company’s drug.
But he said questions remained about where the AstraZeneca drug would be used compared to existing biologics for COPD patients with high eosinophil levels. He said there are no studies that have directly compared AstraZeneca’s treatment to other biologics, so doctors will likely continue to evaluate whether it should be used before or after currently available treatments in these patients once the product is on the market.
She said she would like to see additional subgroup analyzes to help make these decisions.
“I’m very excited about the data, but I’m encouraging them to look at additional cuts in subgroups of the data to understand what the benefits are for patients so they can make the most informed decisions possible,” she said. “I think it’s a big open question at this point how providers will deal with it and how the GOLD committee will ultimately deal with it.”
Han was referring to the Chronic Obstructive Pulmonary Disease Scientific Committee’s Global Initiative, which is developing and updating international guidelines for the diagnosis, management and prevention of COPD.
Dobber said the drug is currently undergoing regulatory review as a treatment for COPD in major markets, including the European Union and China. It is also being studied in a Phase 2 trial in severe asthma and a Phase 3 trial in severe viral lower respiratory tract disease.
“We truly believe this has the potential to be one of the biggest products ever for respiratory medicine” 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 the leading cause of disease, environmental exposures are important triggers that are often overlooked, he said.
“Not everyone has a history of smoking,” Dobber said, noting that particulates from sources such as wildfire smoke can irritate the lungs, which are “very sensitive organs.”
He said he hopes the attention the new data will bring will raise awareness that COPD is a serious disease and encourage broader efforts to reduce the factors that contribute to it.
