Alkeus Pharmaceuticals receives FDA Rare Pediatric Disease and Fast Track designations for gildeuretinol as treatment for Stargardt disease

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Alkeus Pharmaceuticals announced that gildeuretinol (ALK-001), an investigational oral therapy, has received Rare Pediatric Disease and Fast Track designations from the FDA for the treatment of Stargardt disease.

Oral gildeuretinol acetate (ALK-001) is a new chemical entity designed to reduce the dimerization of vitamin A without modulating the visual cycle. In preclinical studies, gildeuretinol decreased vitamin A dimerization down to the normal rate and prevented retinal degeneration and loss of visual function in animals with Stargardt disease.¹

Michel Dahan, president and CEO of Alkeus Pharmaceuticals, pointed out that Stargardt disease is a progressive rare condition leading to severe vision loss in children and adults, and there is no approved treatment available.

“Receiving both the FDA’s Rare Pediatric Disease and Fast Track designations are important milestones for Alkeus that highlight the potential for oral gildeuretinol to be a groundbreaking therapy for patients,” Dahan said. “These designations were granted on top of the previously awarded Breakthrough Therapy and Orphan Drug designations.”

Dahan added that the achievements recognize the significant unmet medical need in Stargardt disease and the overwhelming burden on patients as well as their families and caregivers.

The FDA grants Rare Pediatric Disease designation to therapeutics intended to treat serious or life-threatening rare diseases in which the serious manifestations primarily affect individuals from birth to 18 years of age. With this designation, Alkeus may be eligible to receive a priority review voucher (PRV) upon approval that could be used to advance another clinical development program. Fast Track designation is granted by the FDA to facilitate the development and expedite the review of drugs intended to treat a serious condition that has clinical data demonstrating the potential to address an unmet medical need. Gildeuretinol has previously received Breakthrough Therapy and Orphan Drug designations from the FDA.

Data from Alkeus’ TEASE program in Stargardt disease were most recently presented during the 2024 American Academy of Ophthalmology annual meeting in October by Christine Nichols Kay, MD, of Vitreo Retinal Associates in Gainesville, Florida.

In TEASE-1, a placebo-controlled, double-masked, randomized 24-month study in patients with Stargardt disease, gildeuretinol slowed the growth rate of atrophic retinal lesions area (square root) by 21.6% compared to untreated patients during the 2-year study.

Gildeuretinol also demonstrated a 29.5% reduction in growth rate of atrophic lesions in a sensitivity analysis using non-transformed values. The growth rates of atrophic retinal lesions were 0.18 mm/year (0.87 mm²/year untransformed area) in the gildeuretinol treated arm, and 0.23 mm/year (1.23 mm²/year) in the untreated arm, mean difference 0.05 mm/year with 95% confidence interval, 0.03 to 0.07, p<0.001. The difference was 0.36 mm²/year using non-transformed analysis with 95% confidence interval, 0.23 to 0.50, p<0.001.¹

In addition, Kay presented interim data from the TEASE-3 study demonstrating that early-stage Stargardt disease patients treated with gildeuretinol showed no disease progression and remained asymptomatic while on therapy for between two and six years. Gildeuretinol treatment in early-stage Stargardt patients was associated with relatively stable visual acuity.

The FDA has granted Rare Pediatric Disease designation to therapeutics intended to treat serious or life-threatening rare diseases that primarily affect individuals from birth to 18 years of age. With this designation, Alkeus may be eligible to receive a priority review voucher (PRV) upon approval, which could be used to expedite the development of another clinical program.¹

The FDA's Fast Track designation is awarded to drugs that are intended to treat serious conditions and have clinical data showing the potential to address an unmet medical need. Gildeuretinol has already received Breakthrough Therapy and Orphan Drug designations from the FDA.

Recent data from Alkeus’ TEASE program in Stargardt disease were presented at the 2024 American Academy of Ophthalmology (AAO) Annual Meeting in October by Christine Nichols Kay, MD, of Vitreo Retinal Associates in Gainesville, Florida.

In the TEASE-1 study, a placebo-controlled, double-masked, randomized 24-month trial in patients with Stargardt disease, gildeuretinol slowed the growth rate of atrophic retinal lesion area (square root) by 21.6% compared to untreated patients. The sensitivity analysis, using non-transformed values, showed a 29.5% reduction in lesion growth. Specifically, the growth rates of atrophic retinal lesions were 0.18 mm/year (0.87 mm²/year untransformed area) in the gildeuretinol-treated group, compared to 0.23 mm/year (1.23 mm²/year) in the untreated group, with a mean difference of 0.05 mm/year (95% CI: 0.03 to 0.07, p<0.001). Using non-transformed analysis, the difference was 0.36 mm²/year (95% CI: 0.23 to 0.50, p<0.001).¹

Kay also presented interim data from the TEASE-3 study, which demonstrated that early-stage Stargardt disease patients treated with gildeuretinol showed no disease progression and remained asymptomatic while on therapy for 2 to 6 years. In these early-stage patients, gildeuretinol treatment was linked with relatively stable visual acuity.

“TEASE-1 is the first randomized, controlled trial in Stargardt disease that has shown an efficacy endpoint, which is very exciting as an inherited retinal disease specialist taking care of patients with this devastating condition,” Kay said. “In addition, the TEASE-3 data indicate the potential value of treating patients with Stargardt disease as early as possible, before onset of progressive central vision loss.”

In both TEASE-1 and TEASE-3, gildeuretinol demonstrated a favorable safety and tolerability profile. There were no adverse events related to hyper- or hypo-vitaminosis A such as xerophthalmia, chromatopsia, dark adaptation delays or night blindness.

Stargardt disease is a serious cause of severe vision impairment in children and young adults, with an estimated 30,000 to 87,000 people affected in the U.S. There is no approved treatment. In individuals with Stargardt disease, the ABCA4 protein is defective. This defect in the protein results in the accelerated dimerization of vitamin A, forming toxic by-products that irreversibly damage the retina, resulting in progressive vision loss.

The Tolerability and Effects of ALK-001 on Stargardt disease (TEASE) studies consist of four independent clinical studies of oral gildeuretinol (ALK-001) in Stargardt disease, denoted as TEASE-1, TEASE-2, TEASE-3 and TEASE-4. The TEASE-1 study was a randomized, double-masked, placebo-controlled trial in 50 patients with Stargardt disease.¹

According to the company, Gildeuretinol met its prespecified primary efficacy endpoint showing a 21.6% reduction in the growth rate of retinal atrophic lesions area (square root) (p<0.001), and a 29.5% reduction for untransformed areas of retinal atrophic lesions against untreated patients. Gildeuretinol was well-tolerated. The TEASE-2 trial is an ongoing, fully enrolled, randomized, double-masked, placebo-controlled trial in 80 patients with moderate Stargardt disease, expected to read out topline data in 2025.

TEASE-3, the first clinical trial in early-stage Stargardt disease, 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 is an open-label extension study.¹

Reference

1. Alkeus Pharmaceuticals Receives FDA Rare Pediatric Disease and Fast Track Designations for Gildeuretinol as a Treatment for Stargardt Disease | Alkeus Pharmaceuticals Inc. Alkeuspharma.com. Published 2023. Accessed November 18, 2024. https://alkeuspharma.com/alkeus-pharmaceuticals-receives-fda-rare-pediatric-disease-and-fast-track-designations-for-gildeuretinol-as-a-treatment-for-stargardt-disease/