Phase 3 NORTHSTAR Trial Launches for Gildeuretinol in Stargardt Disease

Alkeus Pharmaceuticals in a press release¹ announced dosing of the first participant in the NORTHSTAR study (NCT07419334), a pivotal phase 3 global trial evaluating oral gildeuretinol acetate (ALK-001) in patients with advanced Stargardt disease—a rare, progressive inherited retinal dystrophy for which no approved therapy currently exists in the US and Europe. This is an important step in the development of a much-needed treatment for a disease that causes irreversible central vision loss, predominantly in children and young adults.

"There remains a significant unmet need in Stargardt disease, and continued progress in research is important for patients and families affected by this condition," said David R.P. Almeida, MD, principal investigator at Erie Retina Research in Erie, PA, where the first participant received the first dose. "This study demonstrates a shared commitment to better understand the disease and to evaluate gildeuretinol's potential as a treatment for Stargardt disease."

NORTHSTAR Trial Design and Endpoints

NORTHSTAR is a randomized, placebo-controlled, double-masked, 24-month trial designed to evaluate the efficacy, safety, and pharmacokinetics of oral gildeuretinol in patients with advanced Stargardt disease who present with atrophic lesions at baseline. The study aims to enroll approximately 230 participants aged 8 to 45 years across an estimated 55 sites in more than 11 countries. The study design has been agreed upon by both the US Food and Drug Administration (FDA) and the European Medicine Agency (EMA).

The primary endpoint is the rate of atrophic lesion growth from months 6 to 24, measured by fundus autofluorescence. The key secondary endpoint is preservation of visual acuity, assessed using low luminance visual acuity (LLVA), selected for its sensitivity in detecting early functional decline that high-contrast best-corrected visual acuity (BCVA) testing may not capture.

Charles C. Wykoff, MD, PhD, a retina specialist with Retina Consultants of Texas, noted the rationale for these endpoint choices: "Slowing lesion growth reflects preservation of retinal tissue, which is important for maintaining visual function over time. LLVA may serve as a sensitive functional measure beyond high-contrast visual acuity testing and could provide additional insight into clinically meaningful changes that more closely reflect patients' day-to-day experiences."

Disease Burden and Unmet Need

Stargardt disease is the most common hereditary macular dystrophy, affecting an estimated 50,000 to 60,000 individuals in the United States alone, with onset typically in childhood or early adulthood. The condition is caused by biallelic loss-of-function variants in the ABCA4 gene that results in accumulation of toxic vitamin A dimers that irreversibly damage the retina and results in progressive visual loss, according to the press release.

Mechanism of Action and Regulatory Background

ALK-001, a new molecular designed to reduce the dimerization of vitamin A without modulating the visual cycle in Stargardt disease, also has been studied for geographic atrophy secondary to age-related macular degeneration. Gildeuretinol has received Breakthrough Therapy, Rare Pediatric Disease, Fast Track and Orphan Drug designations for Stargardt disease from the FDA. The EMA has designated gildeuretinol as an orphan medicinal product to treat non-syndromic inherited retinal dystrophies due to defects in the ABCA4 gene, which includes Stargardt disease.

According to Alkeus, gildeuretinol has been administered to more than 400 patients treated to date and has exhibited a well-tolerated safety profile observed in patients ranging in age from 8 to 45 years.

Reference
1. Alkeus Pharmaceuticals. First patient dosed in pivotal global phase 3 NORTHSTAR study of oral gildeuretinol in Stargardt disease. GlobeNewswire. June 8, 2026. https://www.globenewswire.com/news-release/2026/06/08/3308130/0/en/alkeus-pharmaceuticals-announces-first-patient-dosed-in-pivotal-global-phase-3-northstar-study-of-oral-gildeuretinol-in-stargardt-disease.html