AAO 2025: The safety and efficacy of oral gildeuretinol in participants with intermediate-stage Stargardt disease

Photo of Philip Ferrone, MD at AAO 2025

The TEASE 2 study represents a critical investigation into potential treatment options for Stargardt disease. In an interview with Philip Ferrone, MD, he shared research exploring gildeuretinol, an experimental drug targeting photoreceptor preservation in moderate disease severity. With no existing treatments available, this study offers hope for those affected by this condition.

By examining ellipsoid zone loss, visual acuity, and patient safety over a 2-year period, researchers aim to understand the drug's potential to slow disease progression. The study's findings could mark a significant milestone in managing this challenging genetic eye disorder.

Note: The following conversation had been lightly edited for clarity.

Ophthalmology Times Europe: What were the key efficacy findings from the trial of oral gildeuretinol in intermediate-stage Stargardt disease, particularly regarding visual function and retinal structure outcomes?

Philip Ferrone, MD: In the TEASE 2 study, which was a study of moderate severity Stargardt's disease, 40 patients were treated with drug, and 39 patients with placebo, and those patients were looked at over a 2-year period. The primary end point for the study was area of ellipsoid zone loss, or photoreceptor loss, effectively. And what was shown when you compare patients treated with drug compared to patients in placebo, there was a 28% reduction in the area of EZ loss in the gildeuretinol-treated groups, so in the drug-treated groups, there was a 28% reduction in the loss of EZ area. That's significant. It was not a significant P, and the reason for that is this study in retrospect was a little bit underpowered. And due to that, despite the curve separating as you go out over the 24 months, it still just did not have the power to be have a P of less than .05. The P was actually 0.2 for this study. That was the primary end point.
The secondary end point of low luminance visual acuity was there was an improvement of 3 fewer letters lost in the treated group compared to the placebo group. And that's a significant result as well, because that was over 2 years and to see any maintenance of visual acuity in these patients that have progressively advancing disease that has no treatment to improve it or stabilize it, is very, very refreshing and impressive.

OTE: How did the safety and tolerability profile of gildeuretinol compare to expectations, and were there any notable systemic or ocular adverse events?

Ferrone: And then a secondary finding as well was there was no difference in microperimetry between the treatment and placebo groups, which microperimetry at least in this patient population is hard to interpret reliably. The average patient age in this study was 21 years old, and these patients had no macular atrophy. They had abnormalities in microperimetry and ellipsoid zone loss, but they were a very varied patient population, even though they're all 'moderate' Stargardt disease, because you could have as little as .4 millimeters squared of EZ loss when you started at baseline. And other patients had 6 millimeters of EZ loss. There was an age range between 8 and 44 years old for the patient population, even though the mean patient age was 21 years of age. An excellent aspect of this drug is how safe it is and how well it's tolerated. There were no abnormalities seen any differently between drug-treated patients and placebo, the placebo group. There also, with regard to chromatopsia or any other visual cycle abnormality, patients had no light dark adaptation. Patients had no symptoms in the treated group, so it was very, very well tolerated, which is what we've seen previously with this drug and other studies, and that was just corroborated in this study.

OTE: Based on these results, how might oral gildeuretinol fit into the current and future treatment landscape for Stargardt disease and other inherited retinal disorders?

Ferrone: This drug was looked at in atrophic AMD, and there was some promising signals there, but focusing on Stargardt's, which is the most common inherited form of juvenile macular dystrophy, about 43,000 patients affected in the US. This drug is great. It reduces the progression, whether you look at atrophy or you look at severely affected patients, moderately affected patients, approximately 22% to 30% and a reduction in progression over 2 years, and there's no treatment right now for Stargardt's disease. It's a terrible disease, has drastic effects on vision in very young people and any treatment, but especially treatment like this that's so safe and so well tolerated and effective is really exciting and fantastic.