Tezspire Achieves Co-Primary Endpoints in Phase 3 Chronic Rhinosinusitis with Nasal Polyps Trial

Amgen and AstraZeneca have announced encouraging top-line results from their Phase 3 WAYPOINT trial for treating chronic rhinosinusitis with nasal polyps (CRSwNP) using TEZSPIRE® (tezepelumab-ekko). The trial revealed that patients treated with TEZSPIRE® experienced a statistically significant and clinically meaningful reduction in nasal polyp size and nasal congestion compared to those receiving a placebo. The safety profile of TEZSPIRE® was consistent with its known characteristics.

The WAYPOINT trial was meticulously designed as a randomized, double-blind, placebo-controlled study to assess the efficacy and safety of TEZSPIRE® in adults suffering from severe CRSwNP. Participants included those who remained symptomatic despite receiving standard treatments like intranasal corticosteroids (INCS). CRSwNP is marked by persistent inflammation of the nasal mucosa and the growth of benign tissues known as nasal polyps, often leading to treatments involving INCS or surgery.

Dr. Joseph Han, vice chair of Rhinology & Endoscopic Sinus and Skull Base Surgery at Eastern Virginia Medical School, US, and a co-primary investigator in the trial, highlighted the significant impact of CRSwNP on patients' daily lives, affecting their smell, taste, sleep, and causing pain and fatigue. He emphasized that the trial's results showcase TEZSPIRE®'s potential as a promising new treatment for this debilitating condition.

Jay Bradner, M.D., executive vice president of Research and Development and chief scientific officer at Amgen, noted that the Phase 3 WAYPOINT results represent a major advancement in improving the lives of those affected by CRSwNP. He pointed out that the data underscores TEZSPIRE®'s unique ability to target multiple inflammatory pathways at the epithelial level, which can provide substantial symptom relief.

Dr. Brian Lipworth, a co-primary investigator from the Scottish Centre for Respiratory Research and Tayside Rhinology Ear, Nose and Throat Clinic, University of Dundee, Scotland, UK, noted the significant burden of CRSwNP on patients, including repeated surgeries and frequent high-dose corticosteroid treatments with serious side effects. He expressed optimism that TEZSPIRE® could offer a new treatment option to reduce this burden.

The full data from the trial will be shared with regulatory authorities and the scientific community at future medical meetings.

The Phase 3 WAYPOINT trial was a rigorous double-blind, multi-center, randomized, placebo-controlled study, involving parallel groups to evaluate the efficacy and safety of TEZSPIRE® in adults with severe CRSwNP. Participants received either TEZSPIRE® or a placebo via subcutaneous injection, followed by a post-treatment follow-up phase lasting 12-24 weeks after the 52-week treatment period. The trial's co-primary endpoints were changes from baseline in total nasal polyp size and bi-weekly mean nasal congestion.

Key secondary endpoints included loss of smell, improvement in disease-specific health-related quality of life (measured by SNOT-22 score), Lund-Mackay score, time to decision for surgery and/or systemic corticosteroids for nasal polyposis, total symptom score from the Nasal Polyposis Symptom Diary, and pre-bronchodilator FEV1 for patients with comorbid asthma and aspirin-exacerbated respiratory disease/NSAID-exacerbated respiratory disease at Week 52.

CRSwNP is a complex inflammatory condition characterized by persistent nasal mucosa inflammation and benign tissue growths known as nasal polyps. These polyps can obstruct nasal passages and cause breathing difficulties, loss of smell, nasal discharge, facial pain, sleep disturbances, and other quality of life impairments. Estimates suggest that up to 56% of CRSwNP patients also have asthma. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine implicated in the shared pathophysiological processes underlying severe asthma and CRSwNP.

Current CRSwNP treatments include various corticosteroids, surgery, and biologic medications.

TEZSPIRE® (tezepelumab-ekko) is a pioneering human monoclonal antibody targeting the primary source of inflammation: the airway epithelium. By blocking TSLP, it prevents the overreactive immune response to various inflammatory triggers associated with severe asthma. TEZSPIRE® is approved for treating severe asthma in multiple countries and is being developed for other indications, including chronic obstructive pulmonary disease and eosinophilic esophagitis.

The Amgen and AstraZeneca collaboration, first established in 2012 and updated in 2020, encompasses the shared development and commercialization responsibilities for TEZSPIRE® in North America, with specific roles for each company in other regions.

The promising results from the Phase 3 WAYPOINT trial suggest that TEZSPIRE® could become a significant new treatment option for patients with chronic rhinosinusitis with nasal polyps, offering hope for improved patient outcomes and quality of life.