Alkeus has dosed the first patient in the global Phase III NORTHSTAR trial testing oral gildeuretinol (ALK-001) for Stargardt disease. The randomised, double-masked, placebo-controlled study will measure atrophic lesion growth by fundus autofluorescence from months 6–24 as its primary endpoint and use low-luminance visual acuity (LLVA) to assess vision preservation. The protocol was agreed with the FDA and EMA, will run at ~55 sites in 11+ countries, and builds on prior safety data and TEASE-3 interim results suggesting slowed disease progression.
Alkeus Doses First Patient in Global Phase III NORTHSTAR Trial of Gildeuretinol for Stargardt Disease
Gildeuretinol has shown a favourable safety profile
Alkeus Pharmaceuticals has dosed the first participant in the pivotal global Phase III NORTHSTAR study evaluating oral gildeuretinol (ALK-001) as a potential treatment for Stargardt disease.
The randomised, double-masked, placebo-controlled trial will assess the safety, efficacy and pharmacokinetics of gildeuretinol in people with advanced Stargardt disease and baseline atrophic lesions. The study protocol — agreed with both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) — is expected to run at roughly 55 sites across more than 11 countries.
Endpoints and Assessments
The primary endpoint compares the growth rate of atrophic lesions measured by fundus autofluorescence (FAF) between months 6 and 24 in the gildeuretinol and placebo groups. FAF imaging will quantify lesion area as a surrogate for retinal cell loss. A key secondary endpoint evaluates preservation of visual function using low-luminance visual acuity (LLVA), a more sensitive measure under dim lighting that may detect functional change earlier than best-corrected visual acuity (BCVA).
Mechanism And Safety
Stargardt disease is caused by defects in the ABCA4 protein, leading to accumulation of toxic vitamin A dimers and progressive, irreversible central vision loss. Gildeuretinol is designed to reduce formation of these toxic dimers without altering the normal visual cycle.
Earlier trials and long-term use have shown a favourable safety profile for gildeuretinol, with no reported cases of chromatopsia, delayed dark adaptation or night blindness and with treatment exposures extending beyond seven years.
Michel Dahan, President and CEO of Alkeus Pharmaceuticals: "We are tremendously excited to begin dosing in our pivotal global Phase III NORTHSTAR study. This represents a meaningful step toward developing a much‑needed treatment for patients affected by this severely debilitating disease. We are particularly encouraged by signals of visual-acuity preservation observed to date, and this programme is designed to demonstrate clinically meaningful outcomes for patients, retina specialists and regulators."
In July 2024, Alkeus reported interim data from the TEASE-3 trial indicating that gildeuretinol acetate slowed progression in early-stage Stargardt disease, supporting advancement to this global Phase III effort.
As the NORTHSTAR trial progresses, investigators will monitor safety, pharmacokinetics and efficacy outcomes to determine whether gildeuretinol can meaningfully slow lesion growth and help preserve vision in people living with Stargardt disease.
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