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Clinical Trial
. 2024 Dec;56(1):2417184.
doi: 10.1080/07853890.2024.2417184. Epub 2024 Oct 28.

Long-term safety of mepolizumab for up to ∼10 years in patients with severe asthma: open-label extension study

Ian Pavord  1 , Robert Chan  2 , Nicola Brown  2 , Peter Howarth  3 , Martyn Gilson  4 , Robert G Price  5 , Jorge Maspero  6
Affiliations
Clinical Trial

Long-term safety of mepolizumab for up to ∼10 years in patients with severe asthma: open-label extension study

Ian Pavord et al. Ann Med. 2024 Dec.

Abstract

Objectives: Long-term safety monitoring of mepolizumab is necessary to support real-world use for the treatment of severe asthma. This Long-Term Access Program assessed the safety and benefit:risk of mepolizumab in pediatric, adolescent, and adult patients with severe asthma.

Materials and methods: This was a multicenter, Phase IIIb safety, open-label extension study of multiple prior studies assessing mepolizumab in addition to standard of care (Aug 2015 - Aug 2022). Adults/adolescents (≥12 years of age) received mepolizumab 100 mg subcutaneously (SC) every 4 weeks until mepolizumab was commercialized. Pediatric patients (6-11 years of age) received mepolizumab 40 mg or 100 mg SC (bodyweight <40 or ≥40 kg, respectively) every 4 weeks. Safety was assessed every 4 weeks and benefit:risk every 12 weeks.

Results: Of the 514 patients enrolled, 57% were female and the mean age was 51.1 (standard deviation: 14.9) years; 24 (5%) patients were 6-17 years of age. Total cumulative mepolizumab exposure across all mepolizumab studies included in this analysis was 1500.59 patient-years; median exposure was 2.03 (range, 0.08 to 9.97) years. Overall, 37 (7%) patients experienced on-treatment serious adverse events (SAEs): 34/502 (7%) in the 100 mg SC group and 3/7 (43%) in the 40 mg SC pediatric group. Two patients experienced SAEs considered to be treatment-related by the investigator. Infections were the most common SAEs of special interest (9 [2%] patients). Physician-assessed benefit:risk of mepolizumab supported continued treatment over the study period.

Conclusions: This long-term safety analysis of mepolizumab was consistent with previous reports, with no emerging safety concerns; most patients had a favorable benefit:risk up to ∼10 years.

Clinical trial identifier: NCT00244686 (GSK ID 201956).

Keywords: Long-term access program; mepolizumab; open-label extension; safety; severe asthma with an eosinophilic phenotype.

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Conflict of interest statement

IP reports speaker’s honoraria for sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, and GSK; payments for organizing educational events from AstraZeneca, GSK, Sanofi/Regeneron, and Teva; honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia, Chiesi, and Knopp; payments to support US Food and Drug Administration approval meetings from GSK; sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, AstraZeneca, Teva, and Chiesi; a grant from Chiesi to support a Phase II clinical trial in Oxford. He is co-patent holder of the rights to the Leicester Cough Questionnaire and has received payments for its use in clinical trials from Merck, Bayer, and Insmed.

JM consulted for AstraZeneca, Sanofi, and Teva, was a speaker for GSK, Menarini, Novartis, and Uriach, and received research grants from Novartis.

RC, NB, PH, MG, and RGP are employees of GSK and hold financial equities in GSK.

Figures

Figure 1.
Figure 1.
(a) Time to study withdrawal in the open-label extension and (b) physician assessment of benefit:risk ratio. Kaplan–Meier estimates of time to withdrawal from study. Patients are represented from Day 1 to the day of withdrawal from study. *1 patient reported an unknown (missed) benefit:risk assessment at Week 48. †In five patient cases (Weeks 12, 24, 144 and 156 [same individual], 168, and 324), physicians decided the benefit:risk ratio was negative. Where a negative benefit:risk ratio was identified by the treating physician, the patient was subsequently withdrawn from the study. SC: subcutaneous.
Figure 2.
Figure 2.
Mepolizumab exposure in the open-label extension and across all mepolizumab clinical studies. SD: standard deviation.
See this image and copyright information in PMC

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