Off-label Fasenra found effective for EGPA in real-world setting

Asthma medication led to clinical remission in up to 70% of patients: Data

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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AstraZeneca’s Fasenra (benralizumab), which is approved for a rare type of asthma, led to clinical remission in up to 70% of eosinophilic granulomatosis with polyangiitis (EGPA) patients taking the therapy off-label in the real-world setting.

The therapy was also associated with a reduced daily dose of oral corticosteroids — a standard EGPA treatment that is linked to serious side effects when taken at high doses or for long periods.

These are the findings of a systematic review of real-world studies that were shared by David J. Jackson, MD, PhD, from King’s College London, in a poster presentation at the 2024 American Thoracic Society International Conference, May 17-22, in San Diego.

The poster was titled “Real-World Outcomes of Benralizumab in Eosinophilic Granulomatosis with Polyangitis: A Systematic Literature Review.”

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High unmet medical need in EGPA with limited treatment options

“There is a high unmet medical need in EGPA as there are limited treatment options and not all patients respond to currently available treatments,” Andrew Menzies-Gow, MD, PhD, the global medical head of respiratory biologics at AstraZeneca, wrote in an email to ANCA Vasculitis News.

“Increasing the number of treatment options could help patients reduce chronic high-dose oral corticosteroids (OCS) usage and achieve remission, alleviating the burden of this disease,” Menzies-Gow added.

EGPA is the rarest type of ANCA-associated vasculitis (AAV), a group of autoimmune disorders characterized by inflammation in small blood vessels, eventually causing damage to tissues and organs.

In most AAV patients, self-reactive antibodies, called ANCAs, drive this damaging inflammation, but EGPA patients are rarely positive for these antibodies.

EGPA is marked by the buildup of a type of immune cell, called eosinophils, into masses in small blood vessels, and by symptoms that most commonly affect the lungs and gastrointestinal tract.

“All patients with EGPA have very high levels of eosinophils at some point in their disease, both in … blood and in affected tissues or organs, which is why an eosinophil targeting [therapy] has the potential to help patients with this debilitating disease,” Menzies-Gow said.

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Fasenra approved as add-on treatment for severe eosinophilic asthma

Fasenra, designed to promote the death of eosinophils, is approved in the U.S. and other countries as an add-on maintenance treatment for severe eosinophilic, or eosinophil-related, asthma — also a common EGPA complication.

“Approximately half of patients with EGPA have concomitant, adult-onset severe eosinophilic asthma,” Menzies-Gow said.

The therapy works by suppressing the IL-5 receptor, a protein at the surface of eosinophils that is key for their maturation and survival. Fasenra’s mode-of-action is similar to that of GSK’s Nucala (mepolizumab), which is approved as an add-on therapy for adults with EGPA in the U.S. and for people 6 and older with hard-to-treat EGPA in the European Union.

A previous head-to-head Phase 3 clinical trial, called MANDARA (NCT04157348), demonstrated Fasenra doesn’t fare worse than Nucala at promoting EGPA remission.

In the meantime, a number of real-world studies and case reports testing benralizumab in EGPA have been published.

Now, an international team of researchers, along with AstraZeneca scientists, systematically reviewed studies published between January 2017 and January 2024 that described outcomes of EGPA patients treated with Fasenra in the real-world setting.

A total of 45 studies were included in the final analysis. From these, 32 were case reports involving 41 patients (39% women; mean age of 43 years), and 13 were group studies totaling 339 patients (43%-83% women; age range from 42-56 years).

The proportion of patients positive for ANCAs in group studies varied from 18%-33%, and reached 49% in case reports.

Most patients (85%-100%) had respiratory involvement, and neurological symptoms were the second most prevalent manifestation.

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Most patients previously treated with oral corticosteroids

Patients were previously treated with other medications, most commonly oral corticosteroids (83%-100% in group studies and 95% in case reports). Nucala was given to up to 66% of patients in group studies and 12% of those in case reports. Immunosuppressants were given to about one-third of patients in case reports and in up to 42% of those in group studies.

Failure to achieve disease remission was the reason cited by 64% of the patients in group studies to switch from Nucala to Fasenra, followed by worsening of symptoms that required an increase in immunosuppressants (30% of patients).

In case reports, 40% of patients said they made such a treatment switch due to their asthma persisting, and another 40% due to failure to control symptoms and/or only temporary eosinophil suppression.

Nearly all patients received Fasenra’s approved regimen for severe eosinophilic asthma. Those with this condition “were more likely to be included due to current label and reimbursement,” the researchers wrote.

Four group studies reported one-year rates of disease remission, defined as a zero on the Birmingham Vasculitis Activity Score (BVAS) assessment along with an oral corticosteroid dose no higher than 4 mg.

In the three studies reporting this outcome based on ANCA status, remission rates ranged from 43.5% to 68.4% among ANCA-negative patients, and from 54% to 71% in ANCA-positive patients. The remaining study reported disease remission in 49% of patients.

Treatment with Fasenra led to a marked decrease in oral corticosteroid use both in group studies and case reports, with a considerable proportion of patients achieving complete discontinuation of such treatments.

These benefits were accompanied by an overall reduction in disease activity, as assessed with the BVAS.

Overall, these real-world findings show Fasenra “was associated with significant OCS-sparing effects and improvements in disease activity following a diagnosis of EGPA,” the researchers wrote in the poster.