One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study

Abstract

Objective

To assess the long-term safety of tezepelumab in Japanese patients with severe uncontrolled asthma.

Methods

This phase III, 52-week, open-label, single-arm study (NOZOMI, NCT04048343) evaluated the safety/tolerability of subcutaneous (SC) tezepelumab 210 mg every 4 weeks (Q4W) in Japanese patients aged 12–80 years with severe uncontrolled asthma using medium- to high-dose inhaled corticosteroids and at least one additional asthma controller medication, with/without oral corticosteroids. Exploratory outcomes included efficacy (asthma exacerbations, lung function, and asthma control), pharmacokinetic parameters, and immunogenicity.

Results

Among 65 patients (median age 52 years), 39 (60%) experienced 94 adverse events (AEs; predominantly nasopharyngitis [13/65]) of mild (49.2%), moderate (7.7%), or severe (3.1%) intensity. Two patients had transient injection site erythema related to tezepelumab. Four patients reported serious AEs unrelated to tezepelumab and one AE led to treatment discontinuation. AEs of special interest were infrequent and generally mild/moderate. Apart from a decrease in blood eosinophils (an expected pharmacodynamic effect), no notable trends/clinically relevant changes in hematology, clinical chemistry, or urinalysis parameters were observed. Among exploratory outcomes, tezepelumab was associated with a low annualized asthma exacerbation rate over the study period (0.11/patient-year), improved lung function (mean [standard deviation] change from baseline of 0.075 [0.226] L in pre-dose/pre-bronchodilator forced expiratory volume in 1 s), and better asthma control versus baseline (responder rate: 71.4% at Week 52).

Conclusion

Tezepelumab 210 mg SC Q4W in Japanese patients with severe uncontrolled asthma showed safety/tolerability profiles similar to international data, with low exacerbation rates and improvements in lung function and asthma control.

Keywords:

• Biologic therapy
• chronic respiratory disease
• exacerbation
• immunogenicity
• lung function
• open-label study

Acknowledgements

The authors thank the participants and their families, the study investigators, the clinical site staff, the NOZOMI study team, and all other persons involved in this study. Additionally, the authors wish to acknowledge Dr Keyra Martinez Dunn and Nila Bhana, MSc, of Edanz, Japan, for providing medical writing support, which was funded by AstraZeneca, Japan, through EMC K.K., Japan, in accordance with Good Publication Practice guidelines (https://www.ismpp.org/gpp3).

Authors’ contributions

Hiroshi Okada, Tatsuro Tokiyo, Nobuya Hayashi, Mami Takikawa, Gene Colice, and Gun Almqvist conceptualized the study and developed the methodology. Nobuya Hayashi and Gene Colice conducted the formal analysis. Masaharu Shinkai, Motohiro Ebisawa, Yasushi Fukushima, and Satomi Takeuchi coordinated project administration and resources. Mami Takikawa, Gene Colice, and Gun Almqvist were responsible for supervision and oversight of the study. All authors participated in conducting the research or data/evidence collection, critical review of the manuscript, and approval of the final version. The study sponsor (AstraZeneca) was involved in the study design, data collection, analysis/interpretation of data, and review of the manuscript.

Data sharing statement

Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Declaration of interest

Masaharu Shinkai, Motohiro Ebisawa, Yasushi Fukushima, and Satomi Takeuchi report receipt of funding from AstraZeneca related to the current study. Hiroshi Okada, Tatsuro Tokiyo, Nobuya Hayashi, Mami Takikawa, Gene Colice, and Gun Almqvist are employees of AstraZeneca and hold stock and/or stock options in AstraZeneca.

Funding

This research was funded by AstraZeneca and Amgen.