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Alkeus Pharmaceuticals has made a significant announcement indicating that <a href="https://www.archyde.com/alkeus-pharmaceuticals-receives-fda-designations-for-gildeuretinol-in-stargardt-disease-treatment/" title="Alkeus Pharmaceuticals Receives FDA Designations for Gildeuretinol in Stargardt Disease Treatment”>gildeuretinol (ALK-001), an innovative oral therapy under investigation, has been granted both Rare Pediatric Disease and Fast Track designations by the FDA for its potential use in treating Stargardt disease, a rare genetic disorder leading to progressive vision loss.
The oral formulation of gildeuretinol acetate (ALK-001) represents a novel class of drug designed specifically to inhibit the dimerization of vitamin A, thereby protecting visual function without altering the underlying visual cycle. Preliminary studies have shown that gildeuretinol successfully reduced vitamin A dimerization to normal levels and effectively prevented retinal degeneration and vision loss in animal models diagnosed with Stargardt disease.
Michel Dahan, the president and CEO of Alkeus Pharmaceuticals, emphasized the dire circumstances faced by patients with Stargardt disease, a progressive condition that can result in severe visual impairment in both children and adults. Currently, there are no FDA-approved treatments for this debilitating condition.
Dahan also highlighted the importance of these designations as they reflect the substantial unmet medical need for effective therapies in Stargardt disease, addressing the considerable burden experienced by patients, their families, and caregivers dealing with this challenging condition.
Recently, data from Alkeus’ TEASE program focused on Stargardt disease were presented at the 2024 American Academy of Ophthalmology annual meeting, with Dr. Christine Nichols Kay from Vitreo Retinal Associates in Gainesville, Florida, detailing the findings.
In the TEASE-1 study, which was rigorously designed as a placebo-controlled, double-masked trial lasting 24 months, it was determined that gildeuretinol slowed the growth rate of atrophic retinal lesions by 21.6% compared to patients who did not receive treatment during the study period. Furthermore, a sensitivity analysis revealed a remarkable 29.5% reduction in lesion growth, illustrating the drug’s potential efficacy.
For the treated group, the rate of growth in atrophic retinal lesions was measured at 0.18 mm/year (equivalent to an untransformed area of 0.87 mm²/year), whereas the untreated group experienced a rate of 0.23 mm/year (1.23 mm²/year), resulting in a mean difference of 0.05 mm/year with a 95% confidence interval of 0.03 to 0.07.
Moreover, Dr. Kay shared interim data from the TEASE-3 study, which provided reassuring evidence that patients with early-stage Stargardt disease treated with gildeuretinol experienced no progression of their condition and remained asymptomatic over treatment durations ranging from two to six years. Among these early-stage patients, the therapy was associated with notably stable visual acuity.
“TEASE-1 marks the first randomized, controlled trial in Stargardt disease that has demonstrated a meaningful efficacy endpoint, which is particularly encouraging for specialists treating patients affected by this serious inherited retinal disease,” stated Kay. “Additionally, findings from the TEASE-3 study underscore the importance of initiating treatment in patients at the earliest stages of Stargardt disease, prior to the onset of significant central vision loss.”
Stargardt disease remains one of the leading causes of severe vision impairment among children and young adults, with estimates suggesting that between 30,000 and 87,000 individuals in the United States are impacted. Currently, there is no approved therapy to address this debilitating condition. The pathophysiology involves a defect in the ABCA4 protein, leading to the rapid dimerization of vitamin A and the formation of toxic by-products that cause irreversible damage to the retina, resulting in progressive vision loss.
The Tolerability and Effects of ALK-001 on Stargardt Disease (TEASE) studies comprise four independent clinical trials exploring the efficacy and safety of oral gildeuretinol (ALK-001) in Stargardt disease—designated TEASE-1, TEASE-2, TEASE-3, and TEASE-4. Specifically, the TEASE-1 trial enrolled 50 patients and was carefully conducted as a randomized, double-masked, placebo-controlled experiment.
According to information released by the company, gildeuretinol met its pre-defined primary efficacy criterion by demonstrating a 21.6% reduction in the rate of growth in retinal atrophic lesion areas during the study.
TEASE-3 is noteworthy as it is the first clinical trial targeting early-stage Stargardt disease and involves an open-label design for patients with genetically confirmed early signs of the condition that are visible through retinal imaging, while they remain symptom-free. TEASE-4 serves as an open-label extension study anticipating further evaluation of the treatment’s long-term effects.
How does gildeuretinol’s mechanism of action differ from traditional treatments for Stargardt disease?
### Interview with Michel Dahan, CEO of Alkeus Pharmaceuticals
**Interviewer:** Thank you for joining us today, Michel. Let’s start with the recent FDA designations for gildeuretinol. How significant are these recognitions for your team and for patients suffering from Stargardt disease?
**Michel Dahan:** Thank you for having me. The Rare Pediatric Disease and Fast Track designations from the FDA are monumental for Alkeus and the Stargardt community. They highlight the urgent need for effective treatments, as currently, there are no FDA-approved options available for this debilitating condition. These designations will expedite our development process and bring us one step closer to providing hope and treatment for patients and their families.
**Interviewer:** Can you explain a bit more about how gildeuretinol works and what sets it apart from other treatments?
**Michel Dahan:** Absolutely. Gildeuretinol is a specialized form of deuterated vitamin A designed to inhibit the dimerization of vitamin A. This is significant because dimerization is known to contribute to retinal degeneration in conditions like Stargardt disease. By protecting visual function without interfering with the visual cycle, gildeuretinol aims to preserve vision in a way that other treatments haven’t been able to achieve.
**Interviewer:** The results from the TEASE program have shown promising efficacy. What were some key takeaways from the recent trial data presented at the American Academy of Ophthalmology meeting?
**Michel Dahan:** The TEASE-1 study was particularly groundbreaking. It was the first randomized, controlled trial in Stargardt disease to demonstrate a meaningful efficacy endpoint. Our data showed that gildeuretinol slowed the growth rate of atrophic retinal lesions by 21.6% compared to the placebo group. This evidence is crucial as it not only validates our approach but also gives physicians new tools to combat this condition.
**Interviewer:** It’s encouraging to hear that early-stage patients showed no progression of their condition over long-term treatment. How does this inform your vision for the future of gildeuretinol?
**Michel Dahan:** Definitely, the findings from the TEASE-3 study are reassuring. They suggest that with early intervention, we may be able to halt disease progression entirely, significantly improving quality of life for these patients. This strengthens our commitment to advancing gildeuretinol through the regulatory process so that it can reach market as quickly as possible.
**Interviewer:** In your opinion, what will gildeuretinol mean for patients and their families experiencing the burden of Stargardt disease?
**Michel Dahan:** Gildeuretinol represents a potential turning point in the management of Stargardt disease. For families, it means the possibility of preserving vision and hope for a better future. Our goal is to alleviate some of the considerable emotional and practical burdens this condition imposes on patients and caregivers. We are excited about the road ahead and are dedicated to making this potential treatment available soon.
**Interviewer:** Thank you, Michel, for sharing these insights. It sounds like you and your team are on an important journey that could transform the lives of many.
**Michel Dahan:** Thank you for the opportunity to discuss our work. We are deeply committed to making a difference in the lives of those affected by Stargardt disease.