AstraZeneca and Amgen have announced positive topline results from the Phase III WAYPOINT trial evaluating Tezspire (tezepelumab) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful reduction in nasal polyp size compared to placebo.
Efficacy and Safety Profile
In addition to the primary endpoint, Tezspire also showed a significant reduction in nasal congestion. The safety profile observed in the WAYPOINT trial was consistent with previous studies of Tezspire, which is already approved for severe asthma. However, specific data from the trial have not yet been released, and will be presented at an upcoming medical congress.
Regulatory Uncertainty
Despite the positive results, William Blair analyst Matt Phipps highlighted a potential regulatory risk. The companies' announcement did not explicitly state their intention to seek approval for Tezspire in CRSwNP. Phipps noted that the FDA approval of Sanofi and Regeneron’s Dupixent (dupilumab) for CRSwNP was supported by two pivotal trials, while WAYPOINT is the only study evaluating Tezspire specifically for this indication.
Mechanism of Action and Market Positioning
Dupixent, a major player in the anti-inflammatory space, targets type-2 inflammation, which is highly prevalent in CRSwNP patients. Tezspire, on the other hand, targets thymic stromal lymphopoietin (TSLP), a cytokine involved in initiating and maintaining allergic, eosinophilic, and other types of inflammation. TSLP signaling is implicated in asthma, chronic obstructive pulmonary disease, and CRSwNP.
Sharon Barri, executive vice president of BioPharmaceuticals R&D at AstraZeneca, stated that the findings reinforce tezepelumab’s mechanism of action, effectively addressing multiple drivers of epithelial-driven inflammatory diseases.
Clinical Implications
While Tezspire may not outperform Dupixent in patients with high type-2 inflammation, its distinct mechanism of action could offer benefits to a subset of patients. Moreover, the co-occurrence of asthma and CRSwNP suggests that including CRSwNP in Tezspire’s label, if approved, could increase its adoption in patients with both conditions.
Competitive Landscape
The positive results for Tezspire follow GSK's announcement in September 2024 regarding its investigational anti-IL-5 antibody depemokimab, which significantly reduced serious asthma attacks. Depemokimab is also being assessed for CRSwNP, with GSK planning regulatory filings for both indications.
