FDA Approves TSLP Inhibitor Tezepelumab for Chronic Rhinosinusitis With Nasal Polyps

The FDA has approved tezepelumab-ekko (Tezspire) as add-on maintenance treatment for inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP) in adults and adolescents aged 12 years and older. The approval, announced October 17, 2025, by Amgen and AstraZeneca, makes tezepelumab the first biologic for CRSwNP that targets thymic stromal lymphopoietin (TSLP)—an epithelial-derived cytokine central to type 2 inflammation.

The decision was based on results from the phase 3 WAYPOINT trial, presented at the 2025 AAAAI/WAO Joint Congress and published simultaneously in The New England Journal of Medicine. The double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of tezepelumab in adults with uncontrolled CRSwNP who received subcutaneous tezepelumab or placebo every 4 weeks for 52 weeks, followed by a 12–24-week observation period.

Coprimary endpoints were change from baseline in endoscopic total Nasal Polyp Score (NPS) and in biweekly mean nasal congestion score, assessed using a validated symptom diary. Key secondary endpoints included loss of smell, SinoNasal Outcome Test (SNOT-22) score, Lund-Mackay score, time to surgery decision or systemic corticosteroid use, and, among participants with comorbid asthma, pre-bronchodilator FEV₁ at week 52.

WAYPOINT Study Findings

Tezepelumab significantly reduced total nasal polyp size and nasal congestion severity compared with placebo, meeting both coprimary endpoints. Improvements were observed as early as week 4 and sustained through week 52.

Participants receiving tezepelumab also demonstrated significant gains in smell and overall disease-specific quality of life, as reflected by improved SNOT-22 and Lund-Mackay scores. The treatment reduced the need for systemic corticosteroids or surgical intervention, and among those with asthma, tezepelumab produced clinically meaningful improvements in lung function (FEV₁).

The safety and tolerability profile was consistent with prior experience in severe asthma, with the most common adverse events being COVID-19, nasopharyngitis, and upper respiratory tract infection.

“For people living with CRSwNP, every breath can feel like a struggle, and many endure years of recurring symptoms and surgeries without significant relief,” Jay Bradner, MD, executive vice president of research and development at Amgen, said in a statement. “The approval of tezepelumab represents a meaningful advance, derived from our longstanding focus on complex inflammatory diseases rooted in epithelial biology.”

CRSwNP affects an estimated 320 million people globally and is characterized by persistent inflammation and benign polyp growth within the nasal cavity, leading to airflow obstruction, congestion, and loss of smell. Despite treatment with intranasal and systemic corticosteroids or repeated sinus surgeries, many patients experience relapse and ongoing symptoms.

“By targeting thymic stromal lymphopoietin (TSLP) at the top of the inflammatory cascade, [tezepelumab] offers a novel option for patients who continue to endure the disruption of this disease despite available treatments,” Joseph Han, MD, vice chair of otolaryngology–head and neck surgery at Old Dominion University and co-primary investigator of the WAYPOINT trial, said. “The FDA approval … brings forward a new treatment option that has demonstrated rapid and sustained symptom improvement, nearly eliminating the need for future surgeries and significantly reducing systemic steroid use.”

A first-in-class human monoclonal antibody, tezepelumab blocks TSLP, a cytokine released by the airway epithelium in response to allergens, viruses, and pollutants. Interruption of this signal dampens multiple inflammatory pathways—including allergic, eosinophilic, and other non–type 2 mechanisms—that drive airway inflammation in both asthma and CRSwNP. Up to 56% of patients with CRSwNP also have comorbid asthma, reflecting shared epithelial dysfunction and inflammation.

Tezepelumab (marketed as Tezspire) is already approved in more than 60 countries for the treatment of severe asthma, available as a prefilled pen or auto-injector for self-administration. Ongoing development programs are evaluating tezepelumab in chronic obstructive pulmonary disease (COPD) and eosinophilic esophagitis (EoE), for which it holds FDA Orphan Drug Designation. Regulatory submissions for CRSwNP remain under review in Europe, China, Japan, and other regions.