Patient dosing has begun in a Phase 3 clinical trial investigating the asthma treatment Fasenra (benralizumab) in people with eosinophilic granulomatosis with polyangiitis (EGPA), a subtype of ANCA-associated vasculitis.
AstraZeneca, which markets Fasenra, also announced the start of dosing in two other Phase 3 trials: one in people with hypereosinophilic syndrome (NCT04191304) and one in those with eosinophilic esophagitis (NCT04543409). It also plans to initiate a trial in eosinophilic gastritis/eosinophilic gastroenteritis. These are all rare eosinophilic diseases, or inflammatory disorders caused by the immune cells known as eosinophils.
“This new Phase III trial for Fasenra in another rare eosinophil-driven disease [eosinophilic gastritis] represents an important advancement of our clinical development programme, with the ultimate goal of improving patients’ outcomes,” Mene Pangalos, executive vice president, BioPharmaceuticals R&D at AstraZeneca, said in a press release.
Fasenra is an antibody that targets the interleukin 5 (IL-5) receptor, which is located at the surface of eosinophils. The binding leads to the near-complete elimination of eosinophils in the body by other immune cells.
It is approved as an add-on maintenance therapy for severe eosinophilic asthma, and AstraZeneca is now investigating its potential to treat other eosinophilic diseases as well as chronic obstructive pulmonary disease.
Fasenra was designated an orphan drug by the U.S. Food and Drug Administration (FDA) for the treatment of EGPA, hypereosinophilic syndrome, and eosinophilic esophagitis. This designation aims to speed the development of potential therapies for rare diseases through benefits, such as seven years of market exclusivity and exemption from FDA application fees.
The ongoing EGPA trial, called MANDARA (NCT04157348), is currently enrolling up to 140 adults with relapsing or refractory EGPA across 70 clinical sites in the U.S. Europe, Canada, Israel, and Japan. Site and contact information can be found here.
Participants will be randomly assigned to a single 30 mg dose of Fasenra or three 100 mg doses of Nucala (mepolizumab, by GSK), all delivered via subcutaneous (under-the-skin) injections for 52 weeks.
Patients will continue to receive standard of care treatment — corticosteroids with or without immunosuppressants — throughout the trial, and those who complete its 52 weeks may be eligible to enter an open-label extension part, in which all participants will receive Fasenra for at least one more year.
The trial’s main goal is to assess the proportion of patients who achieve remission at both weeks 36 and 48. Secondary measures include the duration of remission, time to first relapse, and the proportion of patients able to reduce their corticosteroid doses.
Researchers will also investigate the treatment’s safety, how it affects the body, the number of hospitalizations and emergency care visits, among additional outcome measures.
“Based on its eosinophil-depleting mechanism of action, we hope that Fasenra can help address the underlying causes of eosinophilic-driven diseases and the limited treatment options for patients today,” Pangalos added.