Positive Phase III WAYPOINT Trial Results for TEZSPIRE® in Chronic Rhinosinusitis with Nasal Polyps
Significant Reduction in Nasal Polyp Severity and Surgery Needs
TEZSPIRE Phase III Trial Shows Benefits in Chronic Rhinosinusitis with Nasal Polyps
Full results from the Phase III WAYPOINT trial demonstrate that AstraZeneca and Amgen’s TEZSPIRE® (tezepelumab-ekko) significantly reduced nasal polyp severity, the need for subsequent surgery, and systemic corticosteroid use in patients with chronic rhinosinusitis with nasal polyps when compared to a placebo. These findings were published in the New England Journal of Medicine and presented as a late-breaking oral presentation at the American Academy of Allergy Asthma & Immunology/World Allergy Organization (WAO) Joint Congress in San Diego, CA.
Improvement in Nasal Polyp Severity and Nasal Congestion
TEZSPIRE treatment led to significant reductions in nasal polyp severity, measured by the co-primary endpoints of Nasal Polyp Score (NPS) and nasal congestion. At week 52, NPS decreased by -2.065 (95% CI: -2.389, -1.742; p<0.0001), and nasal congestion (measured by the Nasal Congestion Score [NCS]) decreased by -1.028 (95% CI: -1.201, -0.855; p<0.0001) compared to placebo. These improvements were seen as early as week four for NPS and week two for NCS, with effects sustained throughout the study period.
Reduced Need for Surgery and Corticosteroids
TEZSPIRE treatment also resulted in statistically significant and clinically meaningful improvements across all key secondary endpoints. Notably, TEZSPIRE reduced the need for subsequent nasal polyp surgery by 98% (p<0.0001) and the need for systemic corticosteroid treatment by 88% (p<0.0001) compared to placebo.
Expert Commentary on Trial Outcomes
Dr. Joseph Han, Vice Chair of the Department of Otolaryngology – Head and Neck Surgery at Old Dominion University and co-primary investigator in the trial, stated: “Many patients with nasal polyps face the risk of repeat surgeries and adverse systemic effects from long-term oral corticosteroids. The WAYPOINT results are clinically meaningful, suggesting that tezepelumab could dramatically reduce the burden of nasal polyps by nearly eliminating the need for future surgeries and corticosteroid use.”
Sharon Barr, Executive Vice President of BioPharmaceuticals R&D, highlighted, “The WAYPOINT results demonstrate TEZSPIRE’s potential as a vital treatment option for patients with chronic rhinosinusitis with nasal polyps. With its first-in-class mechanism of action targeting TSLP, these data strengthen the evidence that tezepelumab can transform care for patients with epithelial-driven inflammatory diseases.”
Key Efficacy Endpoints in the WAYPOINT Trial
| Endpoint | Tezepelumab (n=203) | Placebo (n=205) | Difference vs. Placebo (95% CI) |
|---|---|---|---|
| Co-primary endpoints | |||
| Total Nasal Polyp Score (range 0-8) | -2.458 (0.114) | -0.392 (0.118) | -2.065 (-2.389, -1.742) |
| Nasal Congestion Score (range 0-3) | -1.743 (0.062) | -0.715 (0.064) | -1.028 (-1.201, -0.855) |
| Key Secondary Endpoints | |||
| Time to first nasal polyp surgery decision | 0.5 (0.0, 2.5) | 22.1 (16.4, 28.2) | 0.02 (0.00, 0.09) |
| Time to first systemic corticosteroid use | 5.2 (1.1, 14.7) | 18.3 (13.3, 24.1) | 0.12 (0.04, 0.27) |
| Loss of Smell Score (range 0-3) | -1.26 (0.06) | -0.26 (0.06) | -1.00 (-1.18, -0.83) |
| SNOT-22 Total Score (range 0-110) | -45.02 (1.81) | -17.76 (1.84) | -27.26 (-32.32, -22.21) |
| Sinus CT Lund-Mackay Score (range 0-24) | -6.27 (0.24) | -0.55 (0.24) | -5.72 (-6.39, -5.06) |
Safety Profile and Tolerability
TEZSPIRE was generally well tolerated, with a safety profile consistent with its approved indication for severe asthma. The most frequently reported adverse events in the WAYPOINT trial were COVID-19, nasopharyngitis, and upper respiratory tract infections. No clinically meaningful differences in safety were observed between the TEZSPIRE and placebo groups.
Regulatory Status and Future Outlook
TEZSPIRE is already approved for the treatment of severe asthma in over 60 countries, including the US, EU, and Japan. It is available as a pre-filled syringe and auto-injector for self-administration. Regulatory filings for tezepelumab in CRSwNP are currently under review in multiple regions.
Indication and Important Safety Information
TEZSPIRE® (tezepelumab-ekko) is indicated for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma. It is not indicated for the relief of acute bronchospasm or status asthmaticus.
Warnings and Precautions:
- Hypersensitivity Reactions: Cases of rash and allergic conjunctivitis were observed, with postmarketing cases of anaphylaxis.
- Acute Asthma Symptoms: TEZSPIRE should not be used to treat acute asthma symptoms or exacerbations.
- Corticosteroid Dosage: Do not abruptly discontinue corticosteroids when starting TEZSPIRE. Gradual reduction should be under a physician’s supervision.
- Infections: Monitor for helminth infections, as the impact of TEZSPIRE on such infections is unknown.
- Live Attenuated Vaccines: Avoid using live vaccines in patients receiving TEZSPIRE.
Adverse Reactions: Common adverse reactions include pharyngitis, arthralgia, and back pain.
Pregnancy: There are no available data on TEZSPIRE use in pregnant women, and it may affect fetal development, particularly in the third trimester.
TEZSPIRE Phase III Trial Shows Benefits in Chronic Rhinosinusitis with Nasal Polyps
AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca
