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Topline results from the Phase III WAYPOINT trial (NCT04851964) show that Tezspire (tezepelumab-ekko; Amgen and AstraZeneca) produced a clinically meaningful reduction in nasal polyps and congestion in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).1,2 The first-in-class human monoclonal antibody acts on the airway epithelium, which is the primary cause of inflammation and the first point of contact for viruses, allergens, pollutants, and other environmental irritants.
“Chronic rhinosinusitis with nasal polyps negatively impact patients’ daily lives with the obstructions leading to disturbances in smell, taste and sleep, as well as pain and fatigue,” co-primary trial investigator Joseph Han, MD, FARS, FAAOA, vice chair of Rhinology & Endoscopic Sinus and Skull Base Surgery, and Allergy, Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School, said in a press release. “The impressive data from the WAYPOINT trial demonstrate tezepelumab’s potential as a new treatment for patients whose lives are disrupted by this debilitating disease.”1
Tezspire inhibits the thymic stromal lymphopoietin (TSLP), which is an alarmin-class cytokine that acts in the early stages of the inflammatory process. The expression of TSLP is elevated in the airways of patients with asthma and is associated with disease severity.
Tezspire was initially approved in December 2021 as the only biologic indicated for severe asthma with no phenotype or biomarker limitation within its approved label. In February 2023, Tezspire was approved as a pre-filled, single-use pen for patients aged 12 years and older with severe asthma.3
CRSwNP is an inflammatory disorder involving persistent inflammation of the nasal mucosa along with nasal polyps. These polyps may block nasal passages, causing breathing issues, loss of or limited sense of smell, nasal discharge, facial pain, sleep disruption, as well as other adverse effects that inhibit quality of life (QoL).
“Patients diagnosed with nasal polyps continue to experience significant burden including repeat surgeries and frequent treatment with high doses of oral corticosteroids, which are associated with serious systemic side effects,” co-primary trial investigator Brian Lipworth, MD, professor of Allergy and Pulmonology, Scottish Centre for Respiratory Research, and Tayside Rhinology Ear, Nose and Throat Clinic, Ninewells Hospital University of Dundee in Scotland, UK, said in the release. “The tezepelumab data are clinically meaningful and offer patients with nasal polyps hope for a potential new treatment option that may reduce the burden on patients and healthcare systems.”1
The double-blind, multi-center, randomized, placebo-controlled, parallel group WAYPOINT trial analyzed the efficacy and safety of Tezspire in adults with severe CRSwNP compared with placebo administered as a subcutaneous injection. Patients who successfully completed the 52-week treatment regimen were eligible for the post-treatment follow-up period of 12-24 weeks.
The trial’s co-primary endpoints were change in total nasal polyp size from baseline as per endoscopic total Nasal Polyp Score and change in biweekly mean nasal congestion from baseline as per participant-reported Nasal Congestion Score analyzed as part of the daily Nasal Polyposis Symptom Diary.
The trial’s key secondary endpoints included loss of smell; improvement in disease-specific health-related QoL as per SinoNasal Outcome Test score; Lund-Mackay score; time to surgery decision and/or systemic corticosteroids for nasal polyposis; time to nasal polyposis surgery decision; time to systemic corticosteroids for nasal polyposis; Nasal Polyposis Symptom Diary total symptom score and pre-bronchodilator FEV1 in trial participants with comorbid asthma and aspirin-exacerbated respiratory disease/non-steroidal anti-inflammatory-exacerbated respiratory disease at 52 weeks.
The trial’s topline data show a statistically significant and clinically meaningful decrease in nasal polyp size and reduced nasal congestion in patients administered Tezspire vs. placebo. In terms of safety, the profile of Tezspire was consistent with the known profile of the drug, with no new signals reported.
“The top-line results from our Phase III WAYPOINT study represent a significant step forward in our commitment to enhancing the lives of those affected by chronic rhinosinusitis with nasal polyps,” Jay Bradner, MD, executive vice president of Research and Development and chief scientific officer at Amgen, said in the release. “The data highlight tezepelumab’s unique capacity to target multiple inflammatory pathways by acting directly at the epithelium, resulting in meaningful symptom relief that can improve patients’ daily experiences.”1
References
1. Tezspire Met Both Co-Primary Endpoints In Phase 3 Trial For Chronic Rhinosinusitis With Nasal Polyps. News release. Amgen. November 7, 2024. Accessed November 7, 2024. https://www.amgen.com/newsroom/press-releases/2024/11/tezspire-met-both-co-primary-endpoints-in-phase-3-trial-for-chronic-rhinosinusitis-with-nasal-polyps
2. Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis (WAYPOINT). ClinicalTrials.gov. Updated July 31, 2024. Accessed November 7, 2024. https://clinicaltrials.gov/study/NCT04851964?tab=history&a=17
3. Tezspire approved for self-administration in the US with a new pre-filled pen. News release. Amgen; February 2, 2023. Accessed November 7, 2024. https://www.amgen.com/newsroom/press-releases/2023/02/tezspire-approved-for-self-administration-in-the-u-s–with-a-new-pre-filled-pen