Phase 2 trial of imlifidase for AAV-linked respiratory distress begins

Therapy designed to prevent antibody-based immune attacks in patients

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Dosing has begun in a Phase 2 clinical trial of imlifidase, an  antibody-cleaving therapy, in people with ANCA-associated vasculitis (AAV) who have or are at risk of disease-associated acute respiratory distress syndrome (ARDS), Hansa Biopharma, the therapy’s developer, announced.

ARDS, a severe complication of AAV, occurs when too little oxygen to adequately supply tissues arrives in the bloodstream from the lungs due to bleeding into the airways.

The investigator-initiated study, dubbed imlifidARDSe (EudraCT 2021-004706-22) and funded by Hansa, is enrolling up to 10 adults at Charité Universitätsmedizin Berlin, in Germany.

It will follow participants for up to six months to assess the safety and effectiveness of imlifidase — approved in Europe to prevent kidney transplant rejection — when given alongside standard care.

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Trial in people with ANCA-associated vasculitis and bleeding in the lungs

“This is an important step forward in the development of our technology platform and pipeline of drug candidates for rare immunologic diseases and conditions. … We look forward to the results of this study,” Søren Tulstrup, Hansa’s president and CEO, said in a company press release.

“There are very few treatment options to achieve rapid control of disease activity for patients affected by ANCA-associated vasculitis and we believe imlifidase constitutes a promising opportunity for these antibody-related disorders,” added Philipp Enghard, MD, a co-principal study investigator.

An autoimmune disease, AAV is characterized by the production of self-reactive antineutrophil cytoplasmic antibodies, or ANCAs, that ultimately cause inflammation and damage to small blood vessels across the body, but most often in the kidneys and lungs.

When AAV affects the lungs, it can cause blood to leak into the air sacs where gases are exchanged. This prevents the air sacs from filling up with air and getting enough oxygen into circulating blood, a condition called ARDS. Patients often have to be admitted to an intensive care unit and put on a ventilator to help with breathing and with getting the oxygen their body needs to function properly.

Administered directly into the bloodstream by intravenous infusion, imlifidase contains an enzyme of the same name that’s derived from the Streptococcus pyogenes bacterium. It specifically breaks down immunoglobulin G (IgG), the most common antibody class among ANCAs.

As such, the therapy is expected to reduce the antibody-based immune attacks that drive damage in AAV to ease disease severity.

“Imlifidase has the potential to be a powerful candidate as new treatment for ANCA-associated vasculitis, particularly in patients with severely active disease,” Enghard said.

Imlifidase approved in Europe for people at risk of organ rejection

In the European Union and the U.K., the medicine, sold as Idefirix, has conditional approval for use before transplant surgery in adults with IgGs against a donor’s kidney to prevent the immune system from rejecting the organ. Full approval is dependent on positive data from confirmatory trials.

The open-label Phase 2 trial will test how well imlifidase can break down AAV-causing IgGs to ease symptoms in adults, ages 18 to 79, with a diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis — the two most common types of AAV.

Enrolled patients also need to test positive for antibodies against myeloperoxidase or proteinase 3, the main targets of ANCAs, and have evidence of bleeding in the lungs.

All will be treated with imlifidase alongside standard care, which includes immunosuppressive treatments and supportive care.

The trial’s main goal is to assess how many patients achieve seroconversion, or a change from testing positive to testing negative for ANCAs, within 24 hours of an infusion.

Secondary goals include time to seroconversion, one-month survival, duration of an ICU stay, and improvements in lung function, including ARDS resolution, and in kidney function, for up to six months.

“Our lead molecule imlifidase has the potential to address areas of high unmet need in the autoimmune disease space, as demonstrated by our clinical studies in anti-glomerular basement membrane … disease and Guillain-Barré syndrome,” Tulstrup said. Both diseases are caused by self-reactive antibodies.

In the U.S. and Europe, imlifidase has been designated an orphan drug for anti-glomerular basement membrane disease and the prevention of antibody-mediated organ rejection in solid organ transplantation. In the U.S., it holds the same designation as a potential treatment of Guillain-Barré syndrome. This status is meant to accelerate a therapy’s clinical development and regulatory review.