A Phase 2 Multicenter, Double-Masked, Randomized, Placebo-Controlled Study to Investigate the Long Term Safety, Tolerability, Pharmacokinetics and Effects of ALK-001 on the Progression of Stargardt Disease

The purpose of this open-label, multicenter study is to determine the long-term safety, pharmacokinetics and effects of ALK-001 (C20-D3-retinyl acetate) on the progression of Stargardt disease. This study is an extension of NCT02402660 and enrolls participants who are at least 8 years old. Enrollment is by invitation only.
Funding Source - FDA OOPD

开始日期2019-12-20

申办/合作机构

Alkeus Pharmaceuticals, Inc.

NCT03845582 / Active, not recruiting临床3期

A Phase 2/3 Multicenter, Randomized, Double-masked, Parallel-group, Placebo-controlled Study to Investigate the Safety, Pharmacokinetics, Tolerability, and Efficacy of ALK-001 in Geographic Atrophy Secondary to Age-related Macular Degeneration

This is a double-masked, multicenter, randomized, placebo-controlled clinical trial, evaluating the efficacy and safety of ALK-001 in participants with Geographic Atrophy (GA) secondary to age-related macular degeneration (AMD).
Up to 200 participants will receive ALK-001 while up to 100 participants will receive a placebo.

开始日期2019-05-07

申办/合作机构

Alkeus Pharmaceuticals, Inc.

NCT02402660 / Recruiting临床2期

The purpose of this study is to determine the long term safety and tolerability of ALK-001 (C20-D3-retinyl acetate), and to explore the effects of ALK-001 on the progression of Stargardt disease in patients between the ages of 8 and 70 years old.
Funding Source - FDA OOPD

开始日期2015-08-01

申办/合作机构

Alkeus Pharmaceuticals, Inc.

100 项与 Gildeuretinol acetate 相关的临床结果

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100 项与 Gildeuretinol acetate 相关的转化医学

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100 项与 Gildeuretinol acetate 相关的专利（医药）

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116

项与 Gildeuretinol acetate 相关的文献（医药）

2023-11-01·Current medicinal chemistry

Clinical Application and Synthesis Methods of Deuterated Drugs

Article

作者: Rao, Guo-Wu ; Zhang, Wen ; Xu, Xiao-Liang

Abstract::

Many drugs have adverse absorption, distribution, metabolism, and excretory (ADME) properties that prevent their widespread use or limit their use in some indications. In addition to preparation techniques and prodrug strategies, deuterium modification is a viable method for improving ADME properties. Deuterated drugs have attracted increasing attention from the pharmaceutical industry in recent years. To date, two deuterated drugs have been approved by the FDA. 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. Recently (June 9, 2021), donafinil has been listed in China; this result has caused major pharmaceutical companies and the pharmaceutical industry to pay attention to deuterium technology again. 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 II clinical trials. The deuterium strategy has been widely used in pharmaceutical research and has become a hot spot in pharmaceutical research in recent years. 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.

2023-09-27·Journal of clinical medicine

Updates on Emerging Interventions for Autosomal Recessive ABCA4-Associated Stargardt Disease.

Review

作者: Shah, Serena M ; Mangwani-Mordani, Simran ; Wang, Liang ; Gregori, Ninel Z

Autosomal recessive Stargardt disease (STGD1) is an inherited retinal degenerative disease associated with a mutated ATP-binding cassette, subfamily A, member 4 (ABCA4) gene. STGD1 is the most common form of juvenile macular degeneration with onset in late childhood to early or middle adulthood and causes progressive, irreversible visual impairment and blindness. No effective treatment is currently available. In the present article, we review the most recent updates in clinical trials targeting the management of STGD1, including gene therapy, small molecule therapy, and stem cell therapy. In gene therapy, dual adeno-associated virus and non-viral vectors have been successful in delivering the human ABCA4 gene in preclinical studies. 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. Stem cell therapy using human pluripotent stem cell-derived retinal pigment epithelium cells demonstrated long-term safety three years after implantation and visual acuity improvements in the first two years after initiation of therapy. 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.

2021-12-08·Translational vision science & technology3区 · 医学

C20D₃-Vitamin A Prevents Retinal Pigment Epithelium Atrophic Changes in a Mouse Model

3区 · 医学

ArticleOA

作者: Zhang, Dan ; Robinson, Kiera ; Washington, Ilyas

Purpose:

This study aimed to evaluate the contribution of vitamin A dimerization to retinal pigment epithelium (RPE) atrophic changes. Leading causes of irreversible blindness, including Stargardt disease and age-related macular degeneration (AMD), occur as a result of atrophic changes in RPE. The cause of the RPE atrophic changes is not apparent. During the vitamin A cycle, vitamin A dimerizes, leading to vitamin A cycle byproducts, such as vitamin A dimers, in the RPE.

Methods:

To study the consequence of vitamin A dimerization to RPE atrophic changes, we used a rodent model with accelerated vitamin A dimerization, Abca4-/-/Rdh8-/- mice, and the vitamin A analog C20D3-vitamin A to selectively ameliorate the accelerated rate of vitamin A dimerization.

Results:

We show that ameliorating the rate of vitamin A dimerization with C20D3-vitamin A mitigates pathological changes observed in the prodromal phase of the most prevalent retinal degenerative diseases, including fundus autofluorescence changes, dark adaptation delays, and signature RPE atrophic changes.

Conclusions:

Data demonstrate that the dimerization of vitamin A during the vitamin A cycle is sufficient alone to cause the prerequisite RPE atrophic changes thought to be responsible for the leading causes of irreversible blindness and that correcting the dimerization rate with C20D3-vitamin A may be sufficient to prevent the RPE atrophic changes.

Translational Relevance:

Preventing the dimerization of vitamin A with the vitamin A analog C20D3-vitamin A may be sufficient to alter the clinical course of the most prevalent forms of blindness, including Stargardt disease and age-related macular degeneration (AMD).

项与 Gildeuretinol acetate 相关的新闻（医药）

2024-05-08

·GlobeNewswire-Health Care

Alkeus Pharmaceuticals Announces Positive Interim Results Demonstrating No Signs of Disease Progression in Early-Stage Stargardt Disease Patients Treated with Gildeuretinol

TEASE-3 study data in early-stage Stargardt disease patients presented at ARVO 2024 CAMBRIDGE, Mass., May 08, 2024 (GLOBE NEWSWIRE) -- Alkeus Pharmaceuticals, Inc. today announced the presentation of positive interim data from its TEASE-3 study demonstrating that early-stage Stargardt disease patients treated with gildeuretinol acetate showed no disease progression and remained asymptomatic for the duration of therapy ranging between two and six years. Results were presented during the Association for Research in Vision and Ophthalmology (ARVO) 2024 Annual Meeting being held May 5-9 in Seattle. “These exciting results demonstrate the potential of gildeuretinol acetate to prevent vision loss in early-stage Stargardt patients,” said Leonide Saad, Ph.D., President and CEO of Alkeus Pharmaceuticals. “We projected that without treatment, patients in the TEASE-3 study would lose vision, following a similar trajectory of vision loss as their previously-diagnosed siblings with identical ABCA4 genetic mutations. All of us working in our growing Alkeus team are committed to advancing research and having an impact on patients living with vision loss. We look forward to submitting our gildeuretinol data for regulatory review later this year.” 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. Retinal imaging and functional outcome measures were used to assess disease progression. To date the TEASE-3 study has enrolled a total of five patients, who receive gildeuretinol as a once-a-day pill. “Interim results of the TEASE-3 trial demonstrating clinical benefit of gildeuretinol in early-stage Stargardt disease patients are extremely promising,” said Michael B. Gorin, M.D., Ph.D., of the Departments of Ophthalmology and of Human Genetics at the David Geffen School of Medicine at UCLA. “The potential of gildeuretinol to significantly slow disease progression and delay vision loss in young patients is an exciting advancement.” Stargardt disease is a serious cause of blindness in children and young adults, with an estimated 30,000 people affected in the U.S. and more than 150,000 worldwide. 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. About the TEASE Trials The TEASE trials consist of four clinical studies of gildeuretinol acetate (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. Gildeuretinol met its prespecified primary efficacy endpoint showing a 21% reduction in the growth rate of retinal atrophic lesions (p<0.001, square root units, 28% 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 Stargardt disease, expected to read out topline data in 2025. TEASE-3 is an open-label study designed to assess gildeuretinol in early-stage Stargardt patients. TEASE-4 is an open-label extension study. About Gildeuretinol Acetate (ALK-001) Gildeuretinol acetate (ALK-001) is a novel molecule created as a specialized form of deuterated vitamin A designed to reduce the dimerization of vitamin A without disrupting vision. In preclinical studies, gildeuretinol decreased vitamin A dimerization to the normal rate seen in unaffected individuals and prevented retinal degeneration and loss of visual function in animals with Stargardt disease. Gildeuretinol has received breakthrough therapy designation and orphan drug designation from the U.S. Food and Drug Administration. In addition to the TEASE trials, a Phase 3 (SAGA) study of gildeuretinol in 200 patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is expected to read out topline data in 2024. About Alkeus Pharmaceuticals Alkeus Pharmaceuticals, Inc. is a private biopharmaceutical company with headquarters in Cambridge, Mass., backed by institutional investors led by Bain Capital Life Sciences. Founded in 2010, Alkeus is developing therapies for serious diseases of the eye with high unmet need. Alkeus’ breakthrough-designated lead candidate, gildeuretinol acetate (ALK-001), is currently being evaluated in clinical trials for the treatment of Stargardt disease and for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). For further information, please contact: Media RelationsMedia01@alkeuspharma.comWebsite: www.alkeuspharma.com

临床结果临床3期突破性疗法孤儿药

2024-05-01

·BioSpace

Alkeus Pharmaceuticals Announces Presentation of Positive Gildeuretinol Data in Early-Stage Stargardt Patients During the ARVO 2024 Annual Meeting May 5-9

CAMBRIDGE, Mass., May 01, 2024 (GLOBE NEWSWIRE) -- Alkeus Pharmaceuticals, Inc. today announced that new positive data from its TEASE-3 clinical trial of gildeuretinol in teenage and young-adult patients with early-stage Stargardt disease will be presented at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Annual Meeting being held May 5-9 in Seattle. Oral Presentation: Gildeuretinol Arrested Stargardt Disease, The TEASE-3 Study (Michael B. Gorin, M.D., Ph.D., UCLA). Paper Presentation No. 3310, May 7, 2:30 p.m. – 2:45 p.m. PDT; Session 334. Retina/RPW Treatment: New drugs, delivery methods, and mechanism of action; Yakima 1, Seattle Convention Center – Arch Building Posters: Gildeuretinol Rapidly Replaces Plasma Vitamin A, a Phase 1 Trial (Gabrielle DeBartolomeo, Alkeus). May 8, 2:15 p.m. – 4:00 p.m. and 4:15 p.m. – 5:15 p.m. PDT; Poster Session 441. Retina/RPE: New Drugs, Mechanisms of Action, and Toxicity; Poster 5103, Board A0360 Gildeuretinol Enables the Vitamin A Cycle (Hendrik P.N. Scholl, M.D., M.A., Ph.D., Institute of Molecular and Clinical Ophthalmology, Basel). May 9, 11:45 a.m. – 1:30 p.m. and 4:00 p.m. – 5:00 p.m. PDT; Poster Session 535. Retinal Cell Biology; Poster 6438, Board B0987 Industry and Academic Leaders Chose Microperimetry as Most Promising Functional Endpoint for Geographic Atrophy Trials (Monica Hennessey, M.P.H., Alkeus). May 9, 8:00 a.m. – 9:45 a.m. and 4:00 p.m. – 5:00 p.m. PDT; Poster Session 505. AMD–4 (clinical research); Poster 5702, Board B0108 Clinical Research Professionals Advocate for Reduction of Patient Burden in Clinical Trials for Geographic Atrophy (Adam Qu, Alkeus). May 9, 8:00 a.m. – 9:45 a.m. and 4:00 p.m. – 5:00 p.m. PDT; Poster Session 505. AMD-4 (clinical research); Poster 5693, Board B0099 About the TEASE Trials The TEASE trials consist of four clinical studies of gildeuretinol acetate (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 randomized patients with Stargardt disease. Gildeuretinol met its prespecified primary efficacy endpoint showing a 21% reduction in the growth rate of retinal atrophic lesions (p<0.001, square root units, 28% 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 Stargardt disease, expected to read out topline data in 2025. TEASE-3 is an open-label study designed to assess gildeuretinol in early-stage Stargardt patients. TEASE-4 is an open-label extension study. About Gildeuretinol Acetate (ALK-001) Gildeuretinol acetate (ALK-001) is a novel molecule created as a specialized form of deuterated vitamin A designed to reduce the dimerization of vitamin A without disrupting vision. In preclinical studies, gildeuretinol decreased vitamin A dimerization to the normal rate seen in unaffected individuals and prevented retinal degeneration and loss of visual function in animals with Stargardt disease. Gildeuretinol has received breakthrough therapy designation and orphan drug designation from the U.S. Food and Drug Administration. In addition to the TEASE trials, a Phase 3 (SAGA) study of gildeuretinol in 200 patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is expected to read out topline data in 2024. About Alkeus Pharmaceuticals Alkeus Pharmaceuticals, Inc. is a private biopharmaceutical company with headquarters in Cambridge, Mass., backed by institutional investors led by Bain Capital Life Sciences. Founded in 2010, Alkeus is developing therapies for serious diseases of the eye with high unmet need. Alkeus’ breakthrough-designated lead candidate, gildeuretinol acetate (ALK-001), is currently being evaluated in clinical trials for the treatment of Stargardt disease and for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). For further information, please contact: Media Relations Media01@alkeuspharma.com Website:

临床结果临床3期临床1期孤儿药突破性疗法

2024-01-23

·BioSpace

Alkeus Pharmaceuticals Appoints Seemi Khan, M.D., Chief Medical Officer

CAMBRIDGE, Mass., Jan. 23, 2024 (GLOBE NEWSWIRE) -- Alkeus Pharmaceuticals, Inc. today announced that Seemi Khan, M.D., M.P.H., M.B.A., has joined the Company as Chief Medical Officer. “We are thrilled to welcome Dr. Khan to the Alkeus executive team as we pursue our mission to innovate transformative therapies for degenerative eye diseases,” said Leonide Saad, Ph.D., President and CEO at Alkeus. “An accomplished executive, Dr. Khan has a track record in bringing rare disease treatments to patients in need across multiple therapeutic areas.” Prior to joining Alkeus, Dr. Khan served as Chief Medical Officer at Reata Pharmaceuticals through its acquisition by Biogen, where she oversaw all clinical programs from early stage to commercialization. Dr. Khan was instrumental in the approval and launch of the first treatment for Friedreich’s ataxia. Dr. Khan’s experience also includes senior leadership roles at Mitsubishi Tanabe Pharma America, Quark Pharmaceuticals, Abbott and AbbVie. An internist and nephrologist with expertise in rare disease, immunology and rheumatology, she has served as an Assistant Professor of Medicine at Tufts University School of Medicine. She further has received an M.P.H. from Harvard T.H. Chan School of Public Health and an M.B.A. from Brandeis University. "I am excited to join Alkeus, particularly at a time when gildeuretinol has shown promising advancement toward the treatment of Stargardt disease,” Dr. Khan said. “I’m eager to continue building the team to bring significant impact on the lives of individuals confronted with progressive vision loss. My commitment to medical innovation and patient care aligns seamlessly with Alkeus' mission, and I look forward to driving forward this life-changing treatment." About Alkeus Pharmaceuticals Alkeus Pharmaceuticals is a biopharmaceutical company with headquarters in Cambridge, Mass. Co-founded by Leonide Saad, Ph.D. and Ilyas Washington, Ph.D., Alkeus is focused on developing therapies for serious diseases of the eye with high unmet need. Alkeus’ lead candidate, gildeuretinol (ALK-001), is currently being evaluated in clinical trials for the treatment of Stargardt disease and for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). About Gildeuretinol (ALK-001) Gildeuretinol acetate (ALK-001) is a novel molecule created as a specialized form of deuterated vitamin A designed to reduce the dimerization of vitamin A without disrupting vision. In preclinical studies, gildeuretinol decreased vitamin A dimerization to the normal rate seen in unaffected individuals and prevented retinal degeneration and blindness in animals with Stargardt disease. In addition to the TEASE trials, a Phase 3 study of gildeuretinol in 200 patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) has recently been completed and is expected to read out topline data in 2024. Gildeuretinol has received breakthrough therapy designation and orphan drug designation by the U.S. Food and Drug Administration. For further information, please contact: David Setboun, Chief Operating Officer Email: media01@alkeuspharma.com Website:

临床3期高管变更突破性疗法孤儿药临床结果

100 项与 Gildeuretinol acetate 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
年龄相关性黄斑变性	临床3期	美国	Alkeus Pharmaceuticals, Inc.	2019-05-07
地图样萎缩	临床3期	美国	Alkeus Pharmaceuticals, Inc.	2019-05-07
II型糖原贮积病	临床3期	美国	Alkeus Pharmaceuticals, Inc.	2019-05-07
斯塔加特病	临床2期	美国	Alkeus Pharmaceuticals, Inc.	2015-08-01
视网膜变性疾病	临床1期	-	Alkeus Pharmaceuticals, Inc.	2014-04-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


TEASE-3 (Corporate Publications) 人工标引	N/A	斯塔加特病	3	ALK-001	窪壓繭製窪淵齋獵齋鏇(襯鹽鏇顧範鑰簾簾繭餘) = All three patients treated for two years or more have remained free of symptoms and disease progression while taking gildeuretinol. 蓋鬱願衊糧壓製鑰鹹遞 (廠憲鏇衊膚選範夢願繭 )	积极	2024-01-10
NCT02402660 (TEASE-1, Biospace) 人工标引	临床2期	斯塔加特病	50	ALK-001	觸壓觸膚廠願衊廠餘製(遞膚構獵願鏇淵壓淵鑰): Difference(%) = -21, P-Value = <0.001 更多	积极	2023-11-03
NCT02402660 (TEASE-1, Biospace) 人工标引	临床2期	斯塔加特病	50	Placebo		积极	2023-11-03
TEASE (ARVO2016)	临床2期	斯塔加特病	50	ALK-001	築壓醖築鑰淵艱繭艱遞(繭艱餘壓構範鹹鏇積鏇) = 鹽夢繭鏇製顧範構鏇襯壓選繭夢顧餘齋壓襯鏇 (簾顧衊衊壓醖壓艱鹽選 ) 更多	积极	2016-09-01