Astra Zeneca to Resume Rivalry with Old Competitor Following Key Win for FASENRA®

By Rajaneesh K. Gopinath, Ph.D.

The IL-5 receptor alpha binding monoclonal antibody, FASENRA® (benralizumab), is a prescription medicine used in combination with other asthma drugs to control severe asthma. With the latest FDA approval, it becomes the only respiratory biologic that offers the choice of administration at home or a clinic with an eight-week maintenance dosing.

Asthma is a chronic and heterogeneous respiratory disease that is often mild in several people. However, there exists a subgroup of patients who experience severe uncontrolled asthma with symptoms that affects their daily life and could prove life-threatening. Out of them, a small percentage also suffer from treatment-resistant, refractory or difficult-to-treat conditions (3).

Eosinophilic Asthma

While we are still continuing to understand the various aspects of severe asthma, the European Respiratory Society (ERS) and American Thoracic Society (ATS) joint task force have constantly reviewed the definitions and provided guidelines for its evaluation and treatment. They currently define it as a condition that requires treatment with high-dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming uncontrolled or which remains uncontrolled despite this therapy (3). The severe form, such as eosinophilic asthma exhibits phenotypes where high levels of eosinophils could be found in the patient’s blood, sputum, saliva or bronchial biopsy samples.

FASENRA® (benralizumab)

The identification of the patient’s specific inflammatory phenotype is crucial for devising a successful treatment plan. A number of monoclonal antibodies are now available as therapeutic options. FASENRA® (benralizumab) is a monoclonal antibody that binds to the IL-5 receptor alpha and attracts the NK cells to destroy the eosinophils via apoptosis. It is AstraZeneca’s first respiratory biologic, which was approved by the FDA back in 2017, as an add-on maintenance treatment in severe eosinophilic asthma (2).

Last week, Astra Zeneca announced the USFDA approval of the drug for self-administration by the patient or caregiver using an auto-injector called the Fasenra Pen. It is also available as a fixed 30mg subcutaneous injection via a pre-filled, single-use syringe which will be administered at the clinic by a professional. This makes it the first and only respiratory biologic that offers the choice of administration at home or in a doctor’s office with an eight-week maintenance dosing (1).

Clinical Trials That Led to Approval

This approval is a result of two trials; GRECO, a Phase III multicenter, open‑label, 28-week trial, and AMES, a multicenter, randomized, open-label, parallel-group Phase I trial. The former enrolled 120 patients with severe asthma to test for the performance and reliability of the 30mg dose administration of FASENRA® at home or in a clinic and demonstrated that the majority of the administrations were successful. The AMES trial, on the other hand, was conducted in healthy people to compare the pharmacokinetic (PK) exposure following a single 30mg administration either by a pre-filled syringe or a prefilled auto-injector. The PK exposure was found to be comparable between both administrations. Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “Fasenra 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 Fasenra in an even more convenient way, giving US healthcare providers and patients the option of administering Fasenra at home or in a doctor’s office, and making treatment more accessible to patients with severe eosinophilic asthma.”

Close Competitors

FASENRA® is a direct competitor to GSK’s NUCALA® (mepolizumab), which is also a humanized monoclonal antibody that is FDA approved for the treatment of severe eosinophilic asthma by blocking IL-5. Last June, its auto-injector bagged the FDA approval for self-administration, making it the first respiratory biologic to do so 5 . While FASENRA® is administered once every four weeks for the first three doses and once every eight weeks thereafter, NUCALA® must be administered continuously every four weeks. Besides, NUCALA® is administered at a fixed dosage of 100mg subcutaneous injection.

References
1. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2019/fasenra-approved-in-the-us-for-self-administration-in-a-new-pre-filled-auto-injector-the-fasenra-pen-04102019.html
2. https://www.astrazeneca.com/media-centre/press-releases/2017/fasenra-benralizumab-receives-us-fda-approval-for-severe-uncontrolled-eosinophilic-asthma-14112017.html
3. https://www.ncbi.nlm.nih.gov/pubmed/29531957
4. https://www.ncbi.nlm.nih.gov/pubmed/24337046
5. https://www.gsk.com/en-gb/media/press-releases/nucala-mepolizumab-gains-fda-approval-for-two-new-self-administration-options/

Author

Rajaneesh K. Gopinath