Alkeus Pharmaceuticals, Inc. recently announced that the first patient was dosed in the pivotal phase 3 NORTHSTAR study of oral gildeuretinol (ALK-001) for the treatment of Stargardt disease (SD).
Let’s start with ALK-001.
What it is: Oral gildeuretinol acetate is a new molecular entity designed to reduce the dimerization of vitamin A without modulating the visual cycle.
Its proposed indications: For the treatment of SD and geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Notably: The candidate has already received four FDA designations for the SD indication, including:
- Breakthrough Therapy
- Rare Pediatric Disease
- Fast Track
- Orphan Drug
And before we get to this phase 3 news—catch me up on previous clinical trials.
ALK-001 is being investigated for the treatment of SD under the Tolerability and Effects of ALK-001 on Stargardt diseasE (TEASE) program:
- TEASE-1: Randomized, double-masked, placebo-controlled trial in 50 patients with advanced SD (Completed)
- TEASE-2: Randomized, double-masked, placebo-controlled trial in 80 patients with moderate SD (Completed)
- TEASE-3 (NCT02402660): Ongoing clinical trial in early-stage SD; is an open-label study of gildeuretinol in genetically confirmed patients with early signs of disease visible on retinal imaging, but who have not begun experiencing symptoms of vision loss
- TEASE-4 (NCT04239625): Open-label extension study
And what has the clinical data shown?
Looking at the TEASE-1 study, ALK-001 was found to:
- Slow the growth rate of atrophic retinal lesions area by 21.6% versus untreated patients
- Demonstrate a 29.5% reduction in growth rate of atrophic lesions
- 0.18 mm/year (0.87 mm2/year untransformed area) in the ALK-001-treated arm
- 0.23 mm/year (1.23 mm2/year) in the untreated arm
Mean difference: 0.05 mm/year, 95% confidence interval (CI), 0.03 to 0.07, p<0.001
Any other study data to report?
Previous interim data released from the TEASE-3 study demonstrated that there was no disease progression, and all patients remained asymptomatic while on the therapy for between 2 and 6 years.
Moreover: ALK-001 resulted in a 21% reduction in the growth rate of retinal atrophic lesions (p<0.001, square root units, 28% effect for untransformed areas) against untreated patients.
What about safety and tolerability?
Gildeuretinol has been well-tolerated, and there were no reports of chromatopsia, dark adaptation delays, or night blindness—all notably consistent with the drug’s unique mechanism of action that does not disrupt the visual cycle.
Now to this new phase 3 study.
The NORTHSTAR trial (NCT07419334) is a global, randomized, placebo-controlled, double-masked 24-month study designed to assess efficacy, safety, and pharmacokinetics of gildeuretinol in patients with advanced SD and atrophic lesions at baseline.
The participants: Alkeus aims to enroll approximately 230 patients in the study between the ages of 8 and 45, with an estimated 55 sites planned in more than 11 countries.
And the main outcome measures?
The primary endpoint is the rate of growth of atrophic lesions measured by fundus autofluorescence (FAF) from Months 6 to 25 comparing gildeuretinol to placebo.
The key secondary endpoint is the preservation of visual acuity as measured by changes in low luminance visual acuity (LLVA) from baseline to Month 24.
Note: Building on previous anatomical and functional findings across the approximately 400 patients that have received gildeuretinol to date, LLVA will be utilized to evaluate participants’ vision in dim lighting conditions, which is expected to be more sensitive than best-corrected visual acuity (BCVA).
Any comments from the company on this update?
Per study investigator Charles C. Wykoff, MD, PhD, director of research at the Retina Consultants of Texas and : “The inclusion of LLVA as a secondary endpoint is … meaningful, as many patients with SD report challenges functioning in low-light environments, even early in the disease course.”
- “LLVA may serve as a sensitive functional measure beyond high-contrast VA testing and could provide additional insight into clinically meaningful changes that more closely reflect patients’ day-to-day experiences,” he added.
Any other news from Alkeus to be aware of?
Indeed. In May 2025, the company reported additional findings from the phase 3 SAGA clinical trial evaluating ALK-001 for the treatment of GA, namely that it significantly slowed the growth of atrophic retinal lesions in SD by 21.6% compared to the untreated group (p<0.001).
Plus: Statistically significant improvements were observed as well, with gildeuretinol showing 4.4 fewer letters lost (p = 0.031) in LLVA over the 24-month period.
When can we expect updates?
While we currently don’t have exact dates for updates on NORTHSTAR, the estimated primary completion date of the study is October 2029.
As usual, stay tuned for more!