The U.S Food and Drug Administration (FDA) has approved the self-administration of benralizumab in a pre-filled and single-use auto-injector pen, providing physicians and patients with a convenient option for the drug to be administered outside clinical settings.1 Benralizumab is a monoclonal antibody that targets IL-5 receptor alpha (IL-5Rα) on eosinophils and attracts natural killer cells to induce apoptosis.2 It is indicated for the add-on maintenance of patients with eosinophilic asthma (EA), a rare and severe form of asthma.3 The approval was supported by the results from the phase 3 GRECO and phase 1 AMES trial which investigated the usability and pharmacokinetic exposure of benralizumab in an at-home delivery setting.4,5
Benralizumab is the third respiratory biologic approved for the treatment of EA, and second for self-administration in the form of an auto-injector following mepolizumab in August 2019.6 EA is a rare and severe type of asthma that accounts for 5-10% of all asthma patients.2 Symptoms mimic those of typical asthma, however, they are usually exacerbated due to elevated levels of eosinophils which cause inflammation of the entire respiratory system, including the nasal passages and lower airways.7
EA is commonly treated with inhaled and/or oral corticosteroids and biologic therapies that reduce eosinophils in the airways. Benralizumab is indicated as an add-on maintenance treatment of patients with EA aged 12 years or above.3 It is a humanized monoclonal antibody that binds to IL-5Rα on eosinophils. This binding prevents activation of the receptor and biological effects exerted by IL-5, such as eosinophil maturation, chemotaxis, adhesion and degranulation that lead to their accumulation in the respiratory system.2 Benralizumab also binds to natural killer cells which induce eosinophil apoptosis through the release of granzymes and perforins.2
The benralizumab auto-injector is available as a 30mg/mL solution single-dose prefilled syringe and recommended to be administered once every 4 weeks for the first 3 doses, and then once every 8 weeks.3 “Benralizumab is the only respiratory biologic that can be given every eight weeks after the initial loading dose period. Today’s news means we can now offer benralizumab in an even more convenient way, giving US healthcare providers and patients the option of administering benralizumab at home or in a doctor’s office,” Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, commented.1 The auto-injector is now approved both in the US and Europe based on the results of two clinical trials.
The multicenter phase 3 GRECO trial was designed to assess patient- or caregiver-reported functionality and reliability of the auto-injector for at-home administration in 120 patients with severe asthma.4 97% of at-home administrations were successful at week 12 and week 16, and 96% of the devices were evaluated as functional.1,4 AMES was a multicenter randomized phase 1 trial aiming to compare the pharmacokinetic exposure (PK) of benralizumab in pre-filled syringe and auto-injector devices in 180 healthy participants.5 Similar PK was reported between the two delivery systems with consistent eosinophil count depletion observed.5
The approval of benralizumab auto-injector will improve the treatment accessibility for EA patients, as well as several other advantages of auto-injector technologies, such as ensuring dosage accuracy, improving safety and reducing the stigma associated with the injection process.8 Benralizumab is also currently being investigated for the treatment of chronic obstructive pulmonary disease, severe nasal polyposis and other eosinophilic diseases.1
1. FASENRA (benralizumab) Approved in the US for Self-administration in a New Pre-filled Auto-injector, the FASENRA PenTM. https://www.businesswire.com/news/home/20191004005089/en/FASENRA%C2%AE-benralizumab-Approved-Self-administration-New-Pre-filled-Auto-injector. Published October 4, 2019. Accessed November 1, 2019.
2. Pelaia C et al. Benralizumab: From the Basic Mechanism of Action to the Potential Use in the Biological Therapy of Severe Eosinophilic Asthma. Biomed Res Int. 2018;2018. doi:10.1155/2018/4839230
3. FASENRA Summary of Product Characteristics. 2018.
4. Barker P et al. Single-Use Autoinjector Functionality and Reliability for At-Home Benralizumab Administration: GRECO Trial Results. Journal of Allergy and Clinical Immunology. 2019;143(2):AB96. doi:10.1016/j.jaci.2018.12.292
5. Martin UJ et al. Comparison of autoinjector with accessorized prefilled syringe for benralizumab pharmacokinetic exposure: AMES trial results. J Asthma. September 2019:1-9. doi:10.1080/02770903.2019.1663428
6. Nucala receives EU approval for self-administration by patients with severe eosinophilic asthma | GSK. GlaxoSmithKline. https://www.gsk.com/en-gb/media/press-releases/nucala-receives-eu-approval-for-self-administration-by-patients-with-severe-eosinophilic-asthma/. Published August 1, 2019. Accessed November 1, 2019.
7. Walford HH, Doherty TA. Diagnosis and management of eosinophilic asthma: a US perspective. J Asthma Allergy. 2014;7:53-65. doi:10.2147/JAA.S39119
8. Pedersen A. How Autoinjector Technologies Could Change Drug Delivery. MDDI Online. https://www.mddionline.com/how-autoinjector-technologies-could-change-drug-delivery. Published June 6, 2018. Accessed November 1, 2019.