Potential Oral Stargardt Treatment Advances to Phase 3 Clinical Trial

A new emerging oral treatment for Stargardt disease – gildeuretinol acetate (ALK-001) from Alkeus Pharmaceuticals – continues progressing through clinical trials with a first patient in Erie, Pennsylvania dosed with the treatment in the company’s global Phase 3 NORTHSTAR Study. 

The two-year clinical trial will evaluate how well the potential treatment works as well as its safety. Alkeus plans to enroll approximately 230 participants between the ages of 8 and 45 who have advanced Stargardt disease, with about 55 planned sites across more than 11 countries. Patients will be randomly assigned to treatment or placebo arms.

Stargardt disease is the most common form of inherited macular degeneration and is often diagnosed in children or teens. There are no current treatments for the rare pediatric disease, which is estimated to affect nearly 500,000 people globally, based on estimates from European studies.

Upgrading vitamin A to prevent vision cell damage

Patients with Stargardt disease start to lose cells in the macula – the center of the retina –causing growing central vision loss that varies from patient to patient. Stargardt is typically caused by a mutation in the ABCA4 gene, which causes toxic byproducts from the processing of vitamin A to build up and damage the retina, causing vision loss.

Scientists developed gildeuretinol by replacing the hydrogen atoms in vitamin A with a heavier version of hydrogen. The modified version of vitamin A creates less toxic waste build-up compared to the natural form of vitamin A. The goal of gildeuretinol is to preserve vision by slowing down the growth of the lesions – areas where retinal cells have been lost.

The current clinical trial phase will measure lesions to see if the treatment slows down their growth. Clinicians will also determine what effect the emerging treatment has on patients’ vision in dim lighting, measured through low luminance visual acuity tests. Many patients with Stargardt have difficulty functioning in dim-light vision, even early on in the disease.

Building on past clinical trials

Alkeus has treated more than 400 patients in earlier phases of clinical trials for gildeuretinol. Past studies indicate that the treatment has the potential to preserve vision. Alkeus reports that previously treated patients did not develop chromatopsia, dark adaptation delays, or night blindness. The treatment has also been tested in clinical trials for geographic atrophy caused by the advanced form of dry AMD.

Emerging Stargardt treatments benefit from decades of research

Gildeuretinol is one of several potential treatments for Stargardt disease, making its way through clinical trials. The Foundation has helped to build knowledge about Stargardt through a $6 million natural history study. Natural history studies follow patients with diseases for years to map out information about the condition that is invaluable when developing and testing potential treatments like gildeuretinol.

Known as ProgSTAR, the natural history study helped to determine the best way to measure if an emerging treatment for Stargardt works. It added to understanding how the disease progresses so that when clinical trials move to the next phase, clinicians know what kinds of patients to enroll. The ProgSTAR study also created a database of Stargardt patients for future clinical trials, including 365 patients in 10 international clinical centers. Multiple companies developing therapies for Stargardt disease have used data from ProgSTAR to inform their clinical trial design.

Enrolling in the Phase 3 NORTHSTAR study

More information on enrolling in the clinical trial is available through Alkeus. To be eligible for the clinical trial, patients must be between the ages of 8 and 45, have a diagnosis of typical autosomal recessive Stargardt disease, and have genetic test results showing at least one disease-causing variant in the ABCA4 gene. The Foundation’s My Retina Tracker provides free genetic testing to determine gene mutations that may be involved in patients’ retinal diseases.