Results from the phase 3 WAYPOINT trial have revealed breakthrough findings for patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), demonstrating the significant therapeutic potential of tezepelumab. The study's findings were presented as a late-breaking abstract at the 2025 American Academy of Allergy, Asthma, & Immunology (AAAAI) annual meeting.
Significant Clinical Improvements
The trial, led by Dr. Joseph Han from Eastern Virginia Medical School, evaluated tezepelumab, a human monoclonal antibody that targets thymic stromal lymphopoietin, in adult patients with severe CRSwNP. The study randomized 10,408 participants to receive either tezepelumab 210 mg (n=5203) or placebo (n=5205) administered subcutaneously every four weeks over 52 weeks.
The results showed remarkable improvements in primary endpoints. Patients receiving tezepelumab demonstrated significant reductions in total nasal polyp score (least squares mean difference: -2.101; 95% CI: -2.414 to -1.788; P<.0001) and mean nasal congestion score (mean difference: -1.088; 95% CI: -1.261 to -0.915; P<.0001) compared to placebo at week 52.
Comprehensive Symptom Relief
Beyond the primary endpoints, tezepelumab demonstrated broad efficacy across multiple measures. Patients experienced significant improvements in:
- Loss of smell (mean difference: -1.033; 95% CI: -1.204 to -0.863)
- SNOT-22 score (mean difference: -28.434; 95% CI: -33.485 to -23.383)
- Lund-Mackay score (mean difference: -5.392; 95% CI: -6.098 to -4.687)
- Total symptom score (mean difference: -7.235; 95% CI: -8.365 to -6.105)
All secondary endpoints showed statistical significance with P<.0001.
Reduced Need for Surgical Intervention
Perhaps most notably, tezepelumab demonstrated a remarkable 92% reduction in the need for nasal polyp surgery or systemic corticosteroid treatment compared to placebo (hazard ratio: 0.08; 95% CI: 0.03 - 0.17). This substantial reduction in surgical interventions represents a significant advancement in the management of severe CRSwNP.
Safety Profile
The safety profile of tezepelumab proved favorable, with adverse event rates comparable between the treatment and placebo groups. This builds upon the medication's established safety record, following its FDA approval in February 2023 for self-administration in severe asthma patients.
Clinical Impact
These findings represent a significant advancement in the treatment of severe CRSwNP, offering patients a potentially transformative therapeutic option that could substantially reduce the need for surgical intervention while providing comprehensive symptom relief. The rapid onset of improvement, observed as early as weeks 2 and 4 post-treatment, suggests the potential for quick clinical benefit for patients struggling with this challenging condition.
