Shots:
- Could a targeted biologic therapy help address the longstanding unmet needs in hypereosinophilic syndrome (HES)? AstraZeneca’s FASENRA has now received US approval for HES, introducing a once-monthly treatment option for patients living with this rare and often underdiagnosed eosinophilic disorder
- Results from the Phase III NATRON trial showed that FASENRA reduced the risk of first HES flare by 65% vs placebo, delayed time to flare, improved fatigue scores as early as week 4, and demonstrated sustained eosinophil depletion with reduced corticosteroid escalation. The study also highlighted improvements in symptom burden, disease control, and patient-reported quality of life measures
- PharmaShots welcomes James Teague and Princess U. Ogbogu for sharing their insights on the approval, the evolving HES treatment landscape, and the clinical learnings from the NATRON trial in advancing therapies for eosinophil-driven diseases
Saurabh: Congratulations on the US approval of FASENRA for hypereosinophilic syndrome (HES). What does this milestone represent for AstraZeneca and the eosinophilic disease community?
James: The US approval of FASENRA for HES highlights scientific progress in eosinophilic diseases and meaningful advancement for patients who previously had limited options. For AstraZeneca, this milestone reinforces the company’s commitment to addressing eosinophilic inflammation across conditions. For the eosinophilic disease community, it provides a targeted treatment option for a rare and underserved condition, offering the potential to reduce flares and fatigue.
Saurabh: HES remains a rare and often underdiagnosed disorder with limited treatment options. What are the key unmet needs that FASENRA is expected to address for patients and healthcare providers?
James: There are currently few treatment options for HES. It’s important to note that the HES treatment landscape is evolving, and new therapies could provide promising alternatives for people living with this condition. The approval of FASENRA brings a much-needed innovation and new optimism to those living with HES, a complex, debilitating disease. For the first time, clinicians can offer a once-monthly treatment that meaningfully reduces flares and hematologic relapse, while addressing fatigue, a symptom that profoundly impacts patients’ quality of life.
Saurabh: FASENRA is already approved across multiple eosinophilic conditions. How does this latest approval strengthen AstraZeneca’s broader respiratory and immunology portfolio?
James: This approval reinforces AstraZeneca’s leadership across respiratory biologics and underscores the strength of our broader Respiratory and Immunology biologics franchise. FASENRA is a cornerstone of that portfolio and is already transforming care with patients with SEA, EGPA, and now HES, supporting AstraZeneca’s bold ambition is to transform the care of immune-mediated diseases for patients by moving beyond symptom control to long-term remission and one day, a cure.
Rare disease studies often present challenges in diagnosis, recruitment, and trial execution. What were some of the key learnings from the development journey of FASENRA in HES?
The NATRON trial underscored that successful development of a study in HES required rigorous diagnostic criteria, global inclusive recruitment, thoughtful trial design, and patient-centric execution. Together, these learnings highlight the importance of precision, flexibility, and patient-centered approaches in advancing therapies for rare, complex diseases like HES.
Saurabh: How is AstraZeneca advancing awareness, diagnosis, and access initiatives for patients living with rare eosinophilic disorders such as HES?
James: AstraZeneca is advancing care for HES by working alongside key patient advocacy organizations and healthcare professionals to raise awareness of its impact, improving access through a new approved therapy, strengthening the clinical evidence base to support diagnosis, and building a broader ecosystem of eosinophil-targeted treatments within our Respiratory and Immunology portfolio.
Saurabh: Looking ahead, what role is FASENRA expected to play in shaping the future treatment landscape for eosinophil-driven diseases?
James: FASENRA has a strong foundation in eosinophil-driven diseases, and we are proud to serve patients living with severe asthma, EGPA and HES. Looking ahead, we see FASENRA continuing to play an important role in shaping the future treatment landscape, as we work to transform care in respiratory and immune-mediated diseases by moving beyond symptom control toward disease modification, remission and, one day, cure. Supported by our industry-leading portfolio and #1 respiratory pipeline, we remain focused on advancing science and improving outcomes for patients.
Saurabh: Could you elaborate on the mechanism of action of benralizumab and its role in targeting eosinophil-driven inflammation in HES?
Princess: Benralizumab binds directly to the IL-5 receptor alpha and blocks IL-5 activity. Once bound to the receptor, FASENRA attracts natural killer cells, which remove eosinophils through apoptosis.
Saurabh: The Phase III NATRON trial demonstrated a significant reduction in disease flares and worsening. Which efficacy outcomes from the study were considered most impactful?
Princess: In the trial, treatment with FASENRA delayed the time to first HES flare and significantly reduced the risk of first HES flare compared to placebo by 65%, which was the primary efficacy outcome. Secondary outcomes supporting flare reduction and patient benefit included proportion of patients experiencing HES flares, annualized rate of HES flares, and improvement in fatigue.
Saurabh: Beyond flare reduction, how did the clinical program evaluate the impact of FASENRA on symptom burden, disease control, and quality of life in HES patients?
Princess: The trial measured change in PROMIS Fatigue scores, which can impact quality of life in HES patients. Benralizumab significantly improved fatigue compared to placebo, with improvements visible as early as week 4 and sustained through week 24. Disease control was measured through other clinical measures including sustained eosinophil depletion, time to first hematologic relapse, and reduction in need for treatment escalation via corticosteroids. Potential improvements in quality of life were indicated by three patient-reported outcome tools: Short Form-36 version 2 survey, Patient Global Impression of Severity, and Patient Global Impression of Change. In combination, the endpoints demonstrated FASENRA’s benefit to clinically meaningful symptom relief, improved disease control, and enhanced patient-reported quality of life within the trial.
Saurabh: What insights did the NATRON trial provide regarding the safety and tolerability profile of FASENRA in the HES setting?
Princess: The NATRON trial showed that FASENRA is well-tolerated in HES patients, with adverse event and serious adverse event rates comparable to placebo, and a safety profile that aligns with prior experience in other eosinophilic diseases.
About James Teague
Vice President, US Respiratory & Immunology and Vaccine & Immune Therapies, AstraZeneca
James Teague serves as US Vice President for Respiratory, Immunology, Vaccines and Immune Therapies at AstraZeneca, where he leads teams dedicated to delivering innovative medicines that improve patient outcomes.
With broad global experience across the US, EUCAN, China and International Markets, he brings extensive expertise across the product lifecycle, from Phase 2 development through commercialization, spanning respiratory, cardiovascular, oncology and vaccines.
James is passionate about expanding access to care in low- and middle-income countries, advancing screening and diagnostic innovation, and supporting sustainable healthcare solutions.
About Princess U. Ogbogu
Princess U. Ogbogu, Division Chief of Pediatric Allergy, Immunology, and Rheumatology at University Hospitals Rainbow Babies and Children’s Hospital and Case Western Reserve University, Cleveland, OH, and principal investigator of the NATRON trial
Princess Ogbogu, MD, is Director of the Division of Pediatric Allergy, Immunology, and Rheumatology at University Hospitals Rainbow Babies & Children’s and is board certified in allergy and immunology. She earned her medical degree from Northeast Ohio Medical University, completed her residency at University Hospitals Cleveland Medical Center, and her fellowship at the National Institutes of Health.
Prior to joining UH, Dr. Ogbogu served as Division Chief of Allergy and Immunology at The Ohio State University. She has held several national leadership roles, including Chair of the American Board of Allergy and Immunology (ABAI), and serves on committees with ACGME, AAAAI, and ACAAI. Her clinical and research interests include eosinophilic disorders, immune therapeutics, and health disparities.
Dr. Ogbogu has received multiple honors, including recognition by Cleveland Magazine’s Top Doctors and Castle Connolly Exceptional Women in Medicine.
