FDA Approval of Tezspire for Chronic Rhinosinusitis with Nasal Polyps
Tezepelumab (Tezspire) has received FDA approval for the treatment of severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) based on significant improvements in nasal polyp size, nasal congestion, and sinonasal symptoms compared to placebo. 1
Efficacy Data Supporting Approval
In the WAYPOINT trial, tezepelumab demonstrated significant improvements in the total nasal polyp score (mean difference vs. placebo: -2.07) and nasal congestion score (mean difference: -1.03) at 52 weeks (p<0.001 for both) 1
Treatment with tezepelumab significantly improved loss of smell (mean difference: -1.00), SNOT-22 total score (mean difference: -27.26), and Lund-Mackay CT score (mean difference: -5.72) compared to placebo (p<0.001 for all) 1
Tezepelumab dramatically reduced the need for nasal polyp surgery (0.5% vs 22.1% with placebo) and systemic glucocorticoid use (5.2% vs 18.3% with placebo) 1
Mechanism of Action
Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), an epithelial cytokine implicated in the pathogenesis of both asthma and CRSwNP 2
TSLP plays a significant role in type 2 inflammation in both CRSwNP and CRS without nasal polyps (CRSsNP) by activating myeloid dendritic cells and group 2 innate lymphoid cells 3
Tezepelumab inhibits both full-length TSLP and its functional cleavage products that are elevated in nasal polyps 3
Clinical Implications
Tezepelumab joins other biologics (dupilumab, omalizumab, mepolizumab) in the treatment algorithm for severe CRSwNP, particularly for patients who have failed conventional therapies 4
In patients with both severe asthma and CRSwNP, tezepelumab has shown improvements across multiple SNOT-22 domains (sleep, nasal, function, ear/facial, and emotion) 2
Tezepelumab may be particularly beneficial for patients with T2 inflammatory CRS, as it inhibits active forms of TSLP that drive this inflammation pathway 3
Position in Treatment Algorithm
Current guidelines recommend intranasal corticosteroids as first-line therapy for CRSwNP, with short courses of oral corticosteroids for exacerbations 5
Endoscopic sinus surgery is generally indicated when medical therapy fails to control symptoms or when there is severe nasal polyposis with obstruction 5
Biologics including tezepelumab are positioned for patients with severe, uncontrolled CRSwNP who have failed conventional therapies 1, 4
Comparative Efficacy
While direct head-to-head comparisons are limited, a comparative review suggests dupilumab may be the most effective biologic for CRSwNP, with tezepelumab now providing an additional option targeting a different inflammatory pathway 6
The WAYPOINT trial results demonstrate tezepelumab's robust efficacy in reducing polyp size, improving symptoms, and decreasing the need for surgery and systemic steroids 1
Safety Considerations
In clinical trials, tezepelumab demonstrated a favorable safety profile for the treatment duration 1
As with other biologics, long-term safety data in CRSwNP is still accumulating, and patient selection should consider comorbidities and potential risks 4
Clinical Pearls
Patients with both severe asthma and CRSwNP may particularly benefit from tezepelumab, as it addresses both conditions simultaneously 2
The significant reduction in need for surgery (0.5% vs 22.1% with placebo) suggests tezepelumab may help avoid invasive procedures in appropriate patients 1
The improvement across multiple symptom domains, including the often difficult-to-treat loss of smell, represents a meaningful clinical benefit for patients 1, 2