Mepolizumab prefilled syringe for the treatment of severe eosinophilic asthma: focus on the pediatric population

ABSTRACT

Introduction

Eosinophil-targeted therapy with mepolizumab for severe eosinophilic asthma has significantly improved asthma control and patient quality of life though administration in children had been restricted to health-care provider reconstitution of a lyophilized powder into a solution with in-clinic administration until recently. Here, we profile the newly FDA-approved use of mepolizumab as a prefilled syringe for the treatment of severe eosinophilic asthma in children aged 6–11 years old, allowing for home administration.

Areas covered

A literature search was conducted on PubMed using keywords such as mepolizumab, severe asthma, eosinophils, IL-5, anti-IL-5, children, pediatric, prefilled syringe, and home administration in several combinations. Published literature through July 2022 including clinical trials and prescribing information for mepolizumab for severe eosinophilic asthma, particularly for use in children and as administration as a prefilled syringe, is reviewed.

Expert opinion

Asthma affects a significant number of children worldwide, and having efficacious, tolerable, targeted precision therapies for this population is crucial. Mepolizumab remains the only targeted anti-IL-5 therapy approved for pediatric asthma down to 6 years of age. The innovation of the prefilled syringe will enable home administration, which would decrease the burden of treatment, and could potentially increase adoption of therapy.

KEYWORDS:

• Mepolizumab
• prefilled syringe
• severe eosinophilic asthma
• anti-IL-5
• pediatric asthma

Article highlights

• Mepolizumab is an IL-5 antagonist monoclonal antibody, first FDA approved in 2015 as an add-on maintenance treatment for severe eosinophilic asthma in patients 12 years and older with administration as a 100 mg subcutaneous solution reconstituted from a lyophilized powder by a health-care provider.

• The 100 mg single-dose prefilled syringe and autoinjector devices became FDA approved for patients 12 years and older in 2019. The 40 mg lyophilized powder reconstituted as a solution also became approved for use in younger children 6–11 years old that same year.

• Most recently, in January 2022 the 40 mg prefilled syringe became approved for younger children 6–11 years old, allowing for home administration by a parent/caregiver.

• Pharmacokinetic studies led to the current dosing recommendations of 100 mg subcutaneously every 4 weeks in patients 12 years and older and 40 mg subcutaneously every 4 weeks in children 6–11 years old.

• Adult studies demonstrated similar bioavailability among mepolizumab 100 mg administered subcutaneously via prefilled syringe, autoinjector, or lyophilized powder reconstituted as a solution. These results of similar pharmacokinetics among the different administration modalities can be extrapolated to the lower 40 mg dose used for younger children.

• The pharmacodynamic response with significant blood eosinophil reduction to around 40–60 cells/μL is similar among children 6–11 years old, adolescents, and adults.

• The pivotal phase III mepolizumab studies demonstrated significant efficacy in reducing asthma exacerbation rates, reducing oral corticosteroid use, as well as improving asthma control and health-related quality of life.

• Efficacy data in children 6–11 years old demonstrated findings similar to adolescent/adult studies with significant reductions in asthma exacerbations (mean 69% reduction on treatment for 1 year with 80% of children experiencing at least 50% reduction) and improved asthma control.

• No significant safety concerns with mepolizumab were identified in clinical trials. The most common adverse reactions include headache, injection site reaction, back pain, and fatigue. Rare hypersensitivity reactions and herpes zoster infections have been reported. Administration via a prefilled syringe has a similar safety profile as the reconstituted lyophilized drug product. The safety profile in younger children aged 6 −11 years is also similar to adolescents/adults.

• Studies demonstrated positive patient treatment experience with self-administration of the 100 mg prefilled syringe with the most liked aspects including ease of use and needle retractability.

• The recent FDA approved mepolizumab 40 mg prefilled syringe for children 6–11 years old with severe eosinophilic asthma allows for parent/caregiver administration at home.

• Mepolizumab home administration may increase convenience and decrease time and costs associated with additional clinic visits; however, medication adherence may be more difficult to track. Shared-decision making should be used to determine the most suitable candidates for home administration.

Declaration of interests

B Geng has disclosures including GSK: Speaker, research support; Sanofi: Speaker, Advisor, research support; Regeneron: Speaker, Advisor, research support; Astra-Zeneca: Advisor and research support; Teva: Speaker and research support; Genentech: Consultant; and Novartis: Consultant and research support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer on this manuscript has participated in advisory boards and conferences by GlaxoSmithKline. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors have substantially contributed to the conception and design of the review article and interpreting the relevant literature and were involved in writing the review article or revised it for intellectual content.

Scientific accuracy review

GlaxoSmithKline provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This paper was not funded.