Once-Daily Gildeuretinol Acetate Could Halt Progression of Early Stargardt Disease

Michael Gorin, MD
Credit: UCLA

New data from the 42nd American Society of Retina Specialists (ASRS) Annual Scientific Meeting suggests the gildeuretinol acetate could pause disease progression in patients with early-stage Stargardt disease.

The presentation of data from the TEASE-3 trial, which is billed by Alkeus Pharmaceuticals as the first clinical trial in early-stage Stargardt disease, detail the effects of gildeuretinol among 3 patients who had been receiving the once-daily oral agent for at least 2 years.^1,2

“The TEASE-3 study has been a unique opportunity to evaluate gildeuretinol in a small group of presymptomatic children for whom we had clinical history information regarding the course of Stargardt disease in older siblings,” said principal investigator Michael B. Gorin, MD, PhD, of the Departments of Ophthalmology and of Human Genetics at the David Geffen School of Medicine at UCLA.² “We were able to assess the ability of the medication to stall vision loss in these children as compared to the age-matched data of their genetically-matched Stargardt siblings. The dramatic delay of vision and photoreceptor loss in this small cohort is an exciting advancement in the therapy for ABCA4-related Stargardt disease and suggests that the clinical benefits may be greater at the earliest stages of this condition.”

For more on gildeuretinol and Stargardt disease, check out this episode of New Insight!

Alkeus Pharmaceuticals TEASE program consists of 4 clinical trials, named TEASE-1, -2, -3, and -4. TEASE-1, which was presented at the during the 2023 American Academy of Ophthalmology (AAO) Retina Subspecialty day, was a randomized . The trial met its primary endpoint, with results indicating use of gildeuretinol acetate, then ALK-001, was associated with a 21% reduction (P <.001) in the growth rate of atrophic retinal lesions compared to the untreated arm and 28% reduction (P <.001) using observed atrophic area.^2,3

TEASE-2 trial is an ongoing, fully enrolled, randomized, double-masked, placebo-controlled trial in 80 patients with Stargardt disease, expected to read out topline data in 2025, and TEASE-4 is an open-label extension trial.^2,3

TEASE-3 is an open-label trial assessing gildeuretinol acetate among patients with early-stage Stargardt disease. The trial’s primary endpoint is disease progression over 2 years, which is assessed by retinal imaging and functional outcome measures. According to Alkeus Pharmaceuticals, a total of 6 patients had been enrolled in the trial as of July 18, 2024.^2,3

At ASRS 2024, Goran presented data from 3 patients within the trial with 2-year data. These patients were aged 13, 17, and 17 years and each had 2 ABCA4 mutations, were exhibiting early signs of maculopathy, and had no complaints of visual impairment.¹

Data presented at the meeting indicated mean retinal sensitivity declined by a mean of 3.1 (SD, 1.5) dB/year during the first year of treatment, but improved at a mean of 0.93 (SD, 0.7) dB/year during the second year of the trial. Further analysis revealed 2 patients had a reduction in photoreceptor area during the first 6 months of treatment, but photoreceptor density increased in the same 2 patients during the 18 months that followed.¹

Investigators highlighted the 3-person cohort’s mean visual acuity was maintained at 88 (SD, 4) ETDRS letters during the 2-year trial. Among 2 patients who completed the 2-year period and were enrolled in the open-label extension trial, visual acuity was preserved for an additional 4 years. Investigators also highlighted there no changes on fundus autofluorescence imaging or serious adverse events during the 2-year trial.¹

“Interim results from the TEASE-3 study of gildeuretinol in early-stage Stargardt patients indicate the potential value of treating patients with confirmed disease-causing ABCA4 genetic mutations as early as possible before the disease causes progressive loss of central vision,” said Seemi Khan, MD, MPH, MBA, chief medical officer of Alkeus Pharmaceuticals.² “There is high unmet need in this disease area with no existing treatment, and we look forward to sharing additional results from this encouraging study in the future as we work to advance our development program, which has the potential to be the first therapy for Stargardt disease."

References:

1. Gorin M. Oral Gildeuretinol Acetate 14 mg Capsules Stalled Stargardt Disease Progression: Updates in the TEASE-3 Study. Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.
2. Alkeus Pharmaceuticals Inc. Alkeus Pharmaceuticals announces presentation of a tease-3 study update showing progression stalled in early-stage stargardt disease patients treated with Gildeuretinol. Alkeus Pharmaceuticals Inc. July 18, 2024. Accessed July 21, 2024. https://alkeuspharma.com/alkeus-pharmaceuticals-announces-presentation-of-a-tease-3-study-update-showing-progression-stalled-in-early-stage-stargardt-disease-patients-treated-with-gildeuretinol/.
3. Alkeus Pharmaceuticals Inc. Alkeus Pharmaceuticals Presents positive gildeuretinol trial results at American Academy of Ophthalmology, demonstrating significant slowing of retinal atrophic lesions in stargardt disease. Alkeus Pharmaceuticals Inc. November 3, 2023. Accessed July 21, 2024. https://alkeuspharma.com/alkeus-pharmaceuticals-presents-positive-gildeuretinol-trial-results-at-american-academy-of-ophthalmology-demonstrating-significant-slowing-of-retinal-atrophic-lesions-in-stargardt-disease/.