gildeuretinol (ALK-001) / Alkeus - LARVOL DELTA

Data from the TEASE-1 study of gildereutinol for Stargardt disease (GlobeNewswire) - P2 | N=160 | TEASE-1 (NCT02402660) | Sponsor: Alkeus Pharmaceuticals, Inc. | "The study showed daily oral gildeuretinol significantly slowed the growth of atrophic retinal lesions in Stargardt disease by a 21.6% reduction versus the untreated group (p<0.001). This treatment effect was maintained across all pre-specified sensitivity analyses. Gildeuretinol was well tolerated and demonstrated a consistent safety profile across all studies to date."

P2 data • Ophthalmology

Alkeus Pharmaceuticals Presents Gildeuretinol Data During the Association for Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting May 4-8, 2025 (GlobeNewswire) - P2/3 | N=220 | SAGA (NCT03845582) | Sponsor: Alkeus Pharmaceuticals, Inc.| "Alkeus Pharmaceuticals, Inc...today announced additional data from its Phase 2 clinical study (SAGA) in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) in which patients treated with oral gildeuretinol had a slower decline in VFQ-25 (vision-related quality of life) and FRI (functional reading independence) index scores compared to placebo at month 24....In SAGA, a placebo-controlled, double masked Phase 2 study of gildeuretinol in GA secondary to AMD, gildeuretinol showed a clinically meaningful trend in slowing GA growth rate of 13.4% from 0 to 24 months (p=0.075), the study’s primary endpoint. In a sensitivity analysis, gildeuretinol showed a statistically significant reduction in the GA lesion growth rate of 15.3% vs. placebo from 6 to 24 months (p=0.047)....The majority of adverse events were mild or moderate."

P2 data • Age-related Macular Degeneration

TEASE-EXT: Open-Label Extension: Tolerability and Effects of ALK-001 on Stargardt Disease (TEASE) (clinicaltrials.gov) - P2 | N=200 | Active, not recruiting | Sponsor: Alkeus Pharmaceuticals, Inc. | Enrolling by invitation ➔ Active, not recruiting | N=140 ➔ 200

Enrollment change • Enrollment closed • Age-related Macular Degeneration • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders

TEASE: Phase 2 Tolerability and Effects of ALK-001 on Stargardt Disease (clinicaltrials.gov) - P2 | N=160 | Enrolling by invitation | Sponsor: Alkeus Pharmaceuticals, Inc. | Trial primary completion date: Dec 2024 ➔ Jun 2026 | Recruiting ➔ Enrolling by invitation | Trial completion date: Mar 2025 ➔ Nov 2026

Enrollment status • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders

Alkeus Pharmaceuticals Announces Presentations of Gildeuretinol Data During the Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting May 4-8, 2025 (GlobeNewswire) - "Alkeus Pharmaceuticals, Inc...today announced that results from its clinical studies of investigational oral gildeuretinol for the treatment of Stargardt disease (TEASE) and geographic atrophy secondary to age-related macular degeneration (SAGA) will be presented at the 2025 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) being held May 4-8 in Salt Lake City."

Clinical data • Age-related Macular Degeneration

Oral Gildeuretinol Treatment in Geographic Atrophy Secondary to AMD in the SAGA Trial: Safety, Efficacy and Patient-reported Outcomes (ARVO 2025) - P3 | "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • Patient reported outcomes • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Safety and Efficacy of Oral Gildeuretinol for Stargardt Disease: TEASE-1 Trial (ARVO 2025) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • Age-related Macular Degeneration • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders

Alkeus Pharmaceuticals Announces Two Presentations of Oral Gildeuretinol Data During the 48th Annual Meeting of the Macula Society Being Held February 12-15, 2025 (GlobeNewswire) - "Alkeus Pharmaceuticals...announced that results from its clinical studies of investigational oral gildeuretinol for the treatment of Stargardt disease (TEASE) and geographic atrophy secondary to age-related macular degeneration (SAGA) will be presented at the 48th Annual Meeting of the Macula Society being held February 12-15 in Charlotte Harbor, Fla."

P2 data • P3 data • Age-related Macular Degeneration • Inherited Retinal Dystrophy

Alkeus Pharmaceuticals Announces New Positive Interim TEASE-3 Study Results Showing Gildeuretinol Prevented Disease Progression in Early-Stage Stargardt Patients (GlobeNewswire) - P2 | N=140 | TEASE (NCT02402660) | Sponsor: Alkeus Pharmaceuticals, Inc. | "Two additional TEASE-3 participants who recently completed 24 months of therapy showed no disease progression, consistent with prior results.A total of five patients have completed the 24-month study. Following the study, these patients have remained on treatment and continue to show no disease progression, with the longest duration of therapy to date being more than seven years.TEASE-3 is the first clinical trial in early-stage Stargardt patients to show no disease progression over multiple years, including preservation of visual acuity.These data will be presented January 14 at 4:30 p.m. PST during the J.P. Morgan Healthcare Conference...'We plan to submit an NDA to the U.S. Food and Drug Administration for gildeuretinol as a treatment for Stargardt disease as soon as possible in 2025 based on compelling data generated to date from our multi-study clinical program.'"

FDA filing • P2 data • Ophthalmology

Alkeus Pharmaceuticals Receives FDA Rare Pediatric Disease and Fast Track Designations for Gildeuretinol as a Treatment for Stargardt Disease (GlobeNewswire) - "Alkeus Pharmaceuticals, Inc...announced that gildeuretinol (ALK-001), an investigational oral therapy, has received Rare Pediatric Disease and Fast Track designations from the U.S. Food and Drug Administration (FDA) for the treatment of Stargardt disease."

Fast track • Ophthalmology

SAGA: Phase 3 Study of ALK-001 in Geographic Atrophy (clinicaltrials.gov) - P3 | N=200 | Completed | Sponsor: Alkeus Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed | N=300 ➔ 200 | Trial completion date: Apr 2024 ➔ Jun 2024

Enrollment change • Trial completion • Trial completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Alkeus Pharmaceuticals Announces Results from the SAGA Study of Oral Gildeuretinol in Patients with Geographic Atrophy Secondary to Age-Related Macular Degeneration (GlobeNewswire) - P3 | N=300 | SAGA (NCT03845582) | Sponsor: Alkeus Pharmaceuticals, Inc. | "Alkeus Pharmaceuticals, Inc. today announced that the SAGA study of oral gildeuretinol acetate (ALK-001) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) demonstrated a reduction of 0.25 sqmm/year vs. placebo (p=0.07) in the primary endpoint of GA lesion growth rate at 24 months. Gildeuretinol demonstrated a statistically significant reduction in the loss of low luminance visual acuity (LLVA) at 24 months (p=0.03). Gildeuretinol showed a favorable safety profile consistent with other studies of gildeuretinol in Stargardt disease. The topline results will be presented as a late breaker at the 128th Annual Meeting of the American Academy of Ophthalmology (AAO) during Retina Subspecialty Day on Friday, October 18, in Chicago."

P3 data • Age-related Macular Degeneration • Ophthalmology

Gildeuretinol Enables the Vitamin A Cycle (ARVO 2024) - "Purpose: Gildeuretinol (formally ALK-001 and C20D3-Vitamin A) is a vitamin A substitute, designed to inhibit the pathological dimerization of vitamin A, a process thought to contribute to the development of Stargardt disease and blindness... Gildeuretinol effectively substituted retinol, and enabled dark adaptation and vision just as retinol would in the vitamin A cycle. Gildeuretinol holds promise as a disease-modifying therapeutic that addresses the underlying cause of Stargardt disease, with the safety profile of a vitamin."

Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Gildeuretinol Rapidly Replaces Plasma Vitamin A, a Phase 1 Trial (ARVO 2024) - "Gildeuretinol (formally ALK-001 and C20D3-Vitamin A) is an investigational therapeutic for Stargardt disease, engineered to replace vitamin A. Gildeuretinol inhibits the pathological dimerization of vitamin A, which is thought to cause Stargardt Disease... Daily oral gildeuretinol acetate 14 mg rapidly replaced plasma vitamin A with gildeuretinol without dietary modification."

P1 data • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Gildeuretinol Arrested Stargardt Disease, The TEASE-3 Study (ARVO 2024) - "In our study, we evaluate the effects of an oral investigational treatment, gildeuretinol (ALK-001), taken once a day, on the progression of pre-symptomatic teenagers diagnosed with Stargardt disease and who have a two-year older symptomatic sibling... In three individuals with presymptomatic Stargardt disease, gildeuretinol arrested vision loss and the progression of retinal pathology. Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details.: Patients diagnosed with a progressive neurodegenerative diseases such as Stargardt disease could benefit more from an early treatment."

Age-related Macular Degeneration • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders • ALK

SAGA: Phase 3 Study of ALK-001 in Geographic Atrophy (clinicaltrials.gov) - P3 | N=300 | Active, not recruiting | Sponsor: Alkeus Pharmaceuticals, Inc. | Trial completion date: Sep 2023 ➔ Apr 2024

Trial completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Open-Label Extension: Tolerability and Effects of ALK-001 on Stargardt Disease (TEASE) (clinicaltrials.gov) - P2 | N=140 | Enrolling by invitation | Sponsor: Alkeus Pharmaceuticals, Inc. | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders

PA025 ALK-001 (C20-D3-Vitamin A) Slows the Growth of Atrophic Lesions in ABCA4-Related Stargardt Disease: Results of a Randomized, Placebo-Controlled Clinical Trial, the TEASE Study (AAO 2023) - No abstract available

Clinical • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Updates on Emerging Interventions for Autosomal Recessive ABCA4-Associated Stargardt Disease. (PubMed, J Clin Med) - "For pharmaceutical therapies ALK-001, deuterated vitamin A shows promise with preliminary data for phase 2 trial, demonstrating a decreased atrophy growth rate after two years...Many other treatment options have ongoing investigations and clinical trials. While multiple potential interventions have shown promise in attenuating disease progression, further exploration is necessary to demonstrate treatment safety and efficacy."

Journal • Review • Age-related Macular Degeneration • Gene Therapies • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders • ALK

Economic Burden and Changing Treatment Landscape in Stargardt Disease: A Literature and Database Review (ISPOR-EU 2023) - "Seven trials investigated 5 drug interventions (emixustat, tinlarebant, STG-001, avacincaptad pegol, ALK-001) with the eighth trial investigating a gene therapy (GT) (vMCO-010). The current healthcare costs associated with SD are not well established. With uncertainty around the current economic burden of SD, it will be difficult to determine the economic impact of new treatment options when making access decisions. Future analysis of analogues from other ocular degeneration disorders may prove useful in determining the current economic burden of SD."

HEOR • Review • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • ALK

Clinical Application and Synthesis Methods of Deuterated Drugs. (PubMed, Curr Med Chem) - "In 2017, austedo was approved by the FDA as a new drug for Huntington's disease in the United States, the first deuterium drug to be marketed worldwide...In addition, BMS-986165, RT001, ALK-001, HC-1119, AVP-786 and other drugs are in phase Ⅲ clinical studies, and some solid deuterium compounds have entered phase I and Ⅱclinical trials...In this paper, the research and development of deuterated drugs are reviewed, and the influence of deuterium modification on drugs, the advantages of deuterium strategies and the synthesis strategies of deuterated drugs are mainly introduced. Hoping to provide references for clinical application, the discovery of new deuterium chemical entities and research and development of new deuterated drugs."

Journal • Huntington's Disease • Movement Disorders

ALK-001 (C20-D3-Vitamin A) Slows the Growth of Atrophic Lesions in ABCA4-Related Stargardt Disease: Results of a Randomized, Placebo-Controlled Clinical Trial, the TEASE Study (AAO 2022) - "In patients with atrophic STGD1, oral administration of ALK-001 safely slowed the growth rate of retinal atrophic lesions."

Clinical • Age-related Macular Degeneration • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders

C20-D3-Vitamin A (ALK-001) in the Treatment of Atrophic Stargardt Disease (Macula 2022) - P2 | "In patients with atrophic STGD1, oral administration of ALK-001 safely slowed the growth rate of retinal atrophic lesions."

Age-related Macular Degeneration • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders

ALK-001 (C20-D3-Vitamin A) slows the growth of atrophic lesions in ABCA4-related Stargardt Disease: Results of a Phase 2 placebo-controlled clinical trial (TEASE study) (ARVO 2022) - "These data represent the first time that a therapeutic intervention slows the progression of STGD1 in a clinically and statistically meaningful way. In addition, the data provides clinical evidence that vitamin A dimers contribute to the pathophysiology of STGD1, and that slowing vitamin A dimerization is beneficial even in advanced stages of STGD1. Layman Abstract: Stargardt disease is a genetic condition that typically leads to central vision loss during one’s childhood or early adulthood."

Clinical • P2 data • Age-related Macular Degeneration • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders • ALK

TEASE: Phase 2 Tolerability and Effects of ALK-001 on Stargardt Disease (clinicaltrials.gov) - P2 | N=140 | Recruiting | Sponsor: Alkeus Pharmaceuticals, Inc. | Trial completion date: Mar 2022 ➔ Mar 2025 | Trial primary completion date: Dec 2021 ➔ Dec 2024

Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders