FDA Approves GSK's Exdensur as Twice-Yearly Add-On Therapy for Severe Asthma

The FDA has approved GSK’s Exdensur (depemokimab-ulaa) as an add-on maintenance therapy for adolescents and adults with severe asthma characterized by an eosinophilic phenotype.¹

FDA Approval of Exdensur and Indicated Patient Population

The regulatory action was based on findings from the Phase III SWIFT-1 (NCT04719832) and SWIFT-2 (NCT04718103) trials,^2,3 which found that twice-yearly dosing of Exdensur significantly lowered annualized asthma exacerbation rates across 52 weeks compared with placebo when added to standard of care.

“Physicians in the US now have the option to provide sustained protection from exacerbations for patients living with severe asthma with an eosinophilic phenotype in just two doses a year,” Kaivan Khavandi, SVP and global head, Respiratory, Immunology & Inflammation R&D, GSK said in a press release. “Exdensur could redefine patient care and further establish the use of biologics for those who continue to experience exacerbations despite treatment.”¹

Exdensur Mechanism of Action

Exdensur, an anti–interleukin (IL)-5 therapy, is the first ultra-long-acting biologic to be evaluated in Phase III trials that demonstrated a binding affinity and high potency for IL-5.³

“[Exdensur] is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5, which potentially enables effective 6-month dosing intervals for patients with asthma,” the authors of a study published by The New England Journal of Medicine wrote. “In a single-dose phase 1 study, researchers found that [Exdensur] had an acceptable safety profile in adult patients with mild or moderate asthma and a blood eosinophil count of at least 200 cells per microliter at screening and led to dose-dependent suppression of the blood eosinophil count that was sustained over a 26-week period.”⁴

Phase III SWIFT-1 and SWIFT-2 Trial Design

• The Phase IIIA SWIFT-1 and SWIFT-2 trials were both, randomized, placebo-controlled replicate studies. Investigators evaluated the efficacy and safety of Exdensur in patients with severe asthma and an eosinophilic phenotype characterized by high eosinophil count and history of exacerbations following unsuccessful treatment with medium- or high-dose inhaled glucocorticoids.
• Investigators enrolled 792 patients, with 762 patients included in the full analysis and randomly assigned in a 2:1 ratio to receive subcutaneous Exdensur [n = 502] at a dose of 100 mg or placebo [n = 260] at weeks zero and 26, along with standard care.
• The trial’s primary endpoint was annualized rate of exacerbations at 52 weeks, with secondary endpoints that included change from baseline in St. George’s Respiratory Questionnaire (SGRQ) score, forced expiratory volume in one second, and asthma symptom reports at 52 weeks.

Exdensur Exacerbation Reduction and Primary Efficacy Results

• Results show that patients administered Exdensur achieved a 58% decrease in the rate of annualized asthma exacerbations across 52 weeks in SWIFT-1 and 48% in SWIFT-2.
• In the SWIFT-1 trial, the annualized rate of exacerbations was 0.46 in the Exdensur cohort compared to 1.11 in the placebo cohort.
• In the SWIFT-2 trial, the annualized rate of exacerbations was 0.56 in the Exdensur cohort compared to 1.08 in the placebo cohort.

“Current biologic treatments for asthma are often underutilized and frequent injections can be inconvenient for many patients and lead to inconsistent use,” Geoffrey Chupp, MD, professor of Medicine, Pulmonary, Critical Care and Sleep Medicine, Yale University said in the press release. “There is clearly an opportunity to provide a longer duration of protection from exacerbations between injections for severe asthma patients that reduces the frequency of doses and may improve overall health care utilization. Exdensur could empower physicians and patients to potentially achieve their treatment goals with fewer injections.”¹

Exdensur Secondary Endpoints and Safety Findings

• In terms of safety, investigators across both trials did not observe a significant between-group difference in the change from baseline in the SGRQ score, and subsequently did not draw statistical inference on the trials’ secondary endpoints.
• In terms of safety, reports of adverse events (AEs) were similar across both cohorts in both SWIFT trials.
• In SWIFT-1, 73% of patients in both cohorts reported AEs. In SWIFT-2, 72% of patients in the Exdensur cohort reported AEs compared to 78% of patients in the placebo cohort.
• No serious AEs or deaths were deemed by investigators to be related to Exdensur.

“The struggle for people living with severe asthma is immense, with many silently enduring continued symptom recurrence and exacerbations,” Tonya Winders, president and CEO, Global Allergy & Airways Patient Platform, said in the release. “An innovative treatment option like Exdensur that offers the long-acting protection from exacerbations that severe asthma patients with an eosinophilic phenotype deserve, with the benefit of fewer doses, is truly welcome.”¹

References

1. Exdensur (depemokimab) approved by US FDA for the treatment of severe asthma. News release. GSK. December 16, 2025. Accessed December 17, 2025. https://www.gsk.com/en-gb/media/press-releases/exdensur-depemokimab-approved-by-us-fda-for-the-treatment-of-severe-asthma/

2. Placebo-controlled Efficacy and Safety Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype (SWIFT-1). ClinicalTrials.gov. Updated December 17, 2024. Accessed December 17, 2025. https://clinicaltrials.gov/study/NCT04719832

3. A Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype (SWIFT-2). ClinicalTrials.gov. Updated November 29, 2024. Accessed December 17, 2025. https://clinicaltrials.gov/study/NCT04718103

4. Jackson D., et al. Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype. N Engl J Med 2024;391:2337-2349. DOI: 10.1056/NEJMoa2406673. Vol. 391 No. 24.