Regulatory Decision Summary for Tezspire (tezepelumab)

The purpose of this Supplement to a New Drug Submission (SNDS) was to obtain a marketing authorization for a new indication for Tezspire for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP).

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterised by inflammatory hyperplastic growths that protrude into the nasal passages. Patients with CRSwNP often experience significant nasal obstruction and congestion, nasal discharge, facial pain or pressure and impaired sense of smell that can have a profound impact on quality of life and function. The standard-of-care for CRSwNP, i.e., intranasal corticosteroids (INCS) and short-term systemic corticosteroids (SCS), and nasal polyp removal may provide symptomatic relief but do not address the underlying inflammatory processes, leading to frequent recurrence, and are associated with side effects. The biologic treatments are used as add-on therapy for CRSwNP when insufficient symptom control from SCS and/or surgery is experienced by the patient. The currently marketed biologics in Canada, still result in inadequate treatment for some patients.

Benefit

A multicentre, randomized, double blind, parallel group, placebo-controlled trial (WAYPOINT) in patients aged 18 years and older with severe CRSwNP inadequately controlled by SCS and/or surgery (n = 408) showed that tezepelumab 210 mg administered by subcutaneous injection every 4 weeks with stable INCS statistically significantly and clinically meaningfully improved total nasal polyp score (NPS) and bi-weekly mean nasal congestion score (NCS) at Week 52 (co-primary endpoints), compared with placebo. Tezepelumab also statistically significantly and clinically meaningfully improved loss of smell, Sino-Nasal Outcome Test (SNOT)-22 score, Lund-Mackay (LMK) score and need for nasal polyp(s) surgery and/or SCS treatment for NP at Week 52 (key secondary endpoints), compared with placebo.

The recommended dose for the treatment of CRSwNP is 210 mg of Tezspire by subcutaneous injection every 4 weeks, which was supported by the clinical trial WAYPOINT.

Risk

Adverse events occurred in 78.3% of tezepelumab-treated patients and 77.1% of placebo-treated patients, with most events being mild to moderate in severity. Serious adverse events were reported in 4.9% of tezepelumab-treated patients and 5.9% of placebo-treated patients.

Important risks identified included serious infections, cardiac events, and malignancies. Five serious infections were reported in the tezepelumab group (2.5%; exposure-adjusted incidence rate [EAIR] 2.5) compared with four in placebo (2.0%; EAIR 2.3), including one case of pulmonary tuberculosis assessed as related to treatment. Serious cardiac events occurred in two tezepelumab-treated patients (acute myocardial infarction and angina pectoris) and three placebo-treated patients; both tezepelumab cases involved individuals with multiple cardiovascular risk factors. Subgroup analyses suggested that older patients (≥65 years) may have a higher numerical incidence of serious adverse events, including cardiac events, although interpretation is limited by small sample size.

Two malignancies were reported in the tezepelumab group (invasive lobular breast carcinoma and malignant melanoma), with none in placebo. No clinically meaningful trends were observed in laboratory parameters, vital signs, or electrocardiograms, except for the expected reduction in eosinophil count. Immunogenicity incidence was low (3%) and had no apparent impact on pharmacokinetics, efficacy, or safety.

Risk mitigation strategies

The identified and potential risks associated with tezepelumab will be managed through labelling, routine pharmacovigilance and implementation of the Risk Management Plan (RMP).

Overall, the benefit-risk profile is favourable for Tezspire (tezepelumab, 110 mg/mL) for the authorized indication: “Tezspire (tezepelumab) indicated as an add-on maintenance treatment with intranasal corticosteroids in adult patients with severe CRSwNP inadequately controlled by systemic corticosteroids and/or surgery” when used under the conditions of use recommended in the authorized Tezspire Product Monograph (PM).

A Notice of Compliance (NOC) is recommended.

The non-annotated PM (dated of 2026-02-04) submitted under the sequence 0073 is acceptable from a clinical perspective.

The labelling material submitted met all applicable regulations and guidance.

For further details about Tezspire, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.