Boehringer advances oral therapy for geographic atrophy

Boehringer Ingelheim has started a proof-of-concept trial of a drug that could offer the first oral treatment for geographic atrophy (GA), a major cause of irreversible sight loss that affects millions of people around the world.

The phase 2 JADE trial is testing the efficacy and safety of BI 1584862, a phospholipid modulator that Boehringer has said could offer a first-in-class treatment for GA, an advanced and severe form of age-related macular degeneration (AMD) characterised by the loss of photoreceptors and retinal pigment epithelial (RPE) cells in the central portion of the retina known as the macula.

At the moment, there are two approved therapies for GA – Apellis' complement C3 inhibitor Syfovre (pegcetacoplan) and Astellas' complement C5 inhibitor Izervay (avacincaptad pegol) – which both have to be administered by injection directly into each of the affected eyes every few weeks.

Both drugs are approved in the US, but are not available in Europe, where marketing applications were submitted but faced resistance from the EU regulator.

"Vision loss associated with geographic atrophy profoundly affects the lives of those impacted, particularly older adults, making daily activities more difficult. The loss of independence has a significant burden for patients, caregivers and society overall," said lead JADE investigator Karl Csaky, head of the Retina Foundation of the Southwest.

"An oral treatment could alleviate the burden of existing treatment regimens and offer the opportunity to address both eyes simultaneously in patients with bilateral disease," he added.

BI 1584862 is thought to work by reducing inflammation associated with GA and preserving vascular function in the retina, said Boehringer. The JADE trial will enrol around 138 people aged 55 and older with at least one eye affected by GA, who will be treated with one of three doses of the drug.

The main outcome measure will be change in the area affected by GA – which tends to cause blind spots in the central vision – while secondary endpoints will include macular thickness and measurement of visual acuity. Results are due in 2026.

Boehringer has made GA one of its R&D priorities, and BI 1584862 is the second candidate in its pipeline to advance into mid-stage clinical testing after BI 771716, an antibody fragment-based therapy that would be delivered by intravitreal injection.

BI 771716 is being compared to Syfovre in the VERDANT trial, with results expected sometime in 2026 or 2027.

Photo by David Underland on Unsplash