AstraZeneca makes consecutive advances in respiratory field, targeting larger COPD market
AstraZeneca has recently made key progress in the respiratory field: Fasenra was approved for EGPA and beat GSK's Nucala head-to-head, demonstrating its strong efficacy against eosinophils. Despite the drug's setback in late-stage COPD trials in 2018, the company is now re-running Phase III trials with stricter eosinophil count-based patient selection, and advancing Tezspire with Amgen, aiming directly at COPD approval in 2026.
Over the past few decades, medications for respiratory diseases such as asthma have made significant progress. Once, patients could only rely on therapies like oral steroids, which came with long-term side effects, for symptomatic treatment. Today, pharmaceutical companies have narrowed their therapeutic targets to more specific directions.
Throughout her career as a pulmonologist, Dr. Donna Carstens has witnessed a complete paradigm shift in respiratory care, from a "treat after failure" approach to targeted therapy. Carstens currently serves as Senior Medical Director of Fasenra, AstraZeneca's biologic.
This strategy directly contributed to Fasenra's approval last month for the rare respiratory disease eosinophilic granulomatosis with polyangiitis (EGPA). The approval was based on a head-to-head study in which Fasenra outperformed GSK's Nucala. Carstens noted that although the EGPA patient population is small, and many of these patients also have severe asthma, this approval demonstrates that Fasenra is a powerful tool in the broader fight against eosinophils. Eosinophils are a type of white blood cell whose elevated levels can trigger inflammation, leading to other respiratory diseases.
In Carstens' view, this reflects Fasenra's flexible applicability in the respiratory field, including difficult-to-treat chronic obstructive pulmonary disease (COPD). Fasenra was first approved in 2017 for severe eosinophilic asthma and has since expanded its indications, but the drug faced setbacks in two late-stage COPD trials in 2018.
However, AstraZeneca is making another push with an ongoing Phase III COPD trial of Fasenra. Carstens said that this time, patients were more selectively screened based on eosinophil counts, allowing the trial to fully leverage Fasenra's strengths. Additionally, the company, along with partner Amgen, is also seeking COPD approval for the biologic Tezspire, providing another opportunity to tackle the disease.
"That's science, that's how it goes. At the end of the day, it comes down to eosinophils."
Dr. Donna Carstens
Senior Medical Director of Fasenra at AstraZeneca
In this interview, Carstens shares how respiratory care is increasingly moving toward precision medicine, how evolving guidelines are improving patient identification, and how earlier COPD trials paved the way for a more comprehensive understanding of the disease.
This interview has been edited for length and style.
Question: How do you view the evolution of the respiratory field over time?
Dr. Donna Carstens: As a pulmonologist practicing since the mid-1990s, I have witnessed an enormous explosion in treatment opportunities for respiratory diseases, especially over the past 10 to 15 years. The old approach of adding inhalers or medications after patients failed treatment—what we called "treat after failure"—has shifted to a "targeted therapy" strategy. Now, we can identify patients with specific treatable traits, focus on the underlying cause, and deliver better, more impactful outcomes for patients.
Question: Did the "targeted therapy" strategy emerge with the wave of biologics in the respiratory field?
The use of biologics has indeed transformed outcomes for many severe patients, but this has also been supported by guidelines continuously updating to keep pace with innovation. For example, the annually updated COPD GOLD guidelines and the asthma GINA report consistently capture the pulse of patient management. In my view, this is the result of science combined with guidelines—guidelines help clinicians understand the right approach, rather than just listening to companies claiming "our drug is best," but managing the disease in an unbiased manner. This has greatly facilitated the adoption of these therapies.
Question: Diseases like EGPA present similarly to other respiratory conditions—how do you overcome the challenge of identifying patients most likely to benefit from drugs like Fasenra?
The biggest challenge is that even in severe asthma, most late-onset patients are actually eosinophilic. And since most asthma patients are managed in primary care settings, when many patients are not referred to specialists, there is a huge problem in awareness of the value of these medications. Therefore, one of our goals is education, helping to understand the guidelines themselves rather than just focusing on brands. Helping primary care understand the different types of disease and their severity is a daunting task. And most patients are on oral steroids, which are very harmful—they cause many problems, and long-term overuse significantly impacts patient outcomes. We have excellent data on steroid reduction and want to change this practice paradigm.
Question: You conducted a head-to-head study of Fasenra against GSK's Nucala. Can you talk about undertaking such a high-risk trial and your confidence at the time?
Since GSK's original study was against placebo, the FDA suggested a head-to-head design (for non-inferiority testing). There was indeed risk, but we were confident in this drug for eosinophil-targeted therapy. Its mechanism of action is more specific in depleting eosinophils. The core belief was that if you can completely deplete rather than just deplete 80%, you are likely to get better results. And that proved to be the case (on the secondary endpoint of patients tapering off oral corticosteroids). When you see that 41% of patients treated with Fasenra were able to completely stop steroids, compared to 26% in the Nucala group, I think that validates its mechanism of action and reinforces our belief.
Question: Speaking of confidence, COPD has frustrated many drug developers, including AstraZeneca. How do you view those difficult trials from a few years ago, and where is the company headed?
That's science, that's how it goes. At the end of the day, it comes down to eosinophils. In our asthma studies, we did not set eosinophil requirements, but at least 70% of severe asthma patients are eosinophilic. COPD is different. What we learned from those Phase III trials is that you have to identify the population that will benefit more. Now, with Sanofi and Regeneron's Dupixent approved for COPD as a biologic targeting the eosinophilic phenotype, we have even more confidence in Fasenra. In our ongoing trial (which has completed enrollment, with data expected next year and, ideally, approval in 2026), we enriched for severe patients with eosinophil counts ≥300, and the trial is an add-on therapy. That's how we learn—learning from science with resilience and belief in the product.
In fact, medicine has evolved. Now we have drugs like Fasenra that target eosinophils, and we are discovering that many COPD patients have eosinophilia. In the past, we did not realize how significant its impact was. Because we now have tools, we are starting to pay attention. If you have a hammer, you go looking for nails. If you don't have a hammer—and we didn't back then—what's the point of looking for nails? We have come a long way in advancing science and following its lead to make a difference for patients.