Drug discovery
32
drugs
With orphan designations
Overview
Stargardt disease is an inherited macular dystrophy caused primarily by biallelic ABCA4 mutations, leading to toxic lipofuscin accumulation in retinal pigment epithelium and photoreceptor degeneration. It manifests as progressive central vision loss, typically emerging in childhood/adolescence, with characteristic yellow retinal flecks. Visual acuity often stabilizes at 20/200–20/400, sparing peripheral vision. Inheritance is usually autosomal recessive, though dominant forms exist (e.g., ELOVL4 mutations). Diagnosis combines fundus imaging, autofluorescence, and genetic testing [1][5][6].
Burden
Visual impairment: 48.7% of eyes develop moderate impairment (>20/70–20/200); 16.5% progress to severe impairment (>20/400) [2][5]
Functional impact: Central vision loss disrupts education/employment, with 47.5% of patients being students [2][13]
Socioeconomic costs: High disability burden due to early-onset, progressive decline, and limited treatments [4][16]
Therapies
Investigational: Visual cycle modulators (emixustat), RBP4 antagonists (tinlarebant), deuterated vitamin A (ALK-001), and optogenetic therapies (MCO-010) [3][7][11]
Gene therapies: RNA exon editors (ACDN-01) and ABCA4 replacement trials underway [11][18]
Supportive care: Low-vision aids, vitamin A restriction, UV-protective lenses [9][17]
Categories: rare genetic diseases, rare ophthalmic disorders
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
retinol binding protein 4 (RBP4) inhibitor | small molecules | FDA | 2026-01-13 | — | Heronova Pharmaceuticals, LLC |
Antisense oligonucleotide against ABCA4 pre-mRNA | oligonucleotides | EMA | 2025-11-21 | — | Astherna B.V. |
Gildeuretinol, gildeuretinol acetate | small molecules | EMA | 2025-08-22 | — | Voisin Consulting |
AAV2.GL-3¿ABCA4 + AAV2.GL-5¿ABCA4 | gene therapies | FDA | 2025-06-18 | — | VeonGen Therapeutics GmbH |
Two AAV vectors, the first expressing the N- and the second expressing the C-region of the ATP-binding cassette subfamily A member 4 (ABCA4) protein fused to N- or C-terminal split-intein sequences | gene therapies | FDA | 2024-04-08 | — | SpliceBio S.L. |
AAV8_ABCA4 RNA Exon Editor | gene therapies | FDA | 2023-11-22 | — | Ascidian Therapeutics, Inc. |
Adeno-Associated Virus Serotype 5 capsid protein containing gene construct encoding human Retinoic Acid Receptor-Related Orphan Receptor Alpha | gene therapies | FDA | 2023-04-26 | — | Ocugen, Inc. |
Vutrisiran [Amvuttra] | RNAs | EMA | 2022-08-10 | — | Alnylam Netherlands B.V. |
Echothiophate iodide | small molecules | FDA | 2022-04-11 | — | Fera Pharmaceuticals, LLC |
Adeno Associate Virus carried Multi Characteristic Opsin | gene therapies | FDA | 2020-12-30 | — | Nanoscope Therapeutics Inc. |
sulfo butyl ether beta-cyclodextrin | small molecules | FDA | 2020-10-08 | — | reVision Therapeutics, Inc. |
Combination of two adeno-associated viral vectors of serotype 8 containing the 5'- and the 3'- half coding sequences of human ABCA4 fused to inteins | gene therapies | EMA | 2019-10-17 | — | Aavantgarde Bio S.r.l. |
Emixustat hydrochloride | small molecules | EMA | 2019-05-29 | — | Pharma Gateway AB |
3-(3-(3,5-bis(trifluoromethyl)phenyl)-1h-pyrazol-1-yl)propanoic acid | small molecules | EMA | 2019-04-24 | — | [INACTIVE] TMC Pharma (EU) Limited |
3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-pyrazol-1-yl) propanoic acid | small molecules | FDA | 2019-04-22 | — | Stargazer Pharmaceuticals, Inc. |
1-(3-{4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl}-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-6-yl)ethan-1-one | small molecules | EMA | 2018-05-25 | — | Voisin Consulting Life Sciences |
soraprazan | small molecules | FDA | 2017-12-22 | — | Katairo GmbH |
tinlarebant | small molecules | FDA | 2017-09-19 | — | Belite Bio, LLC |
emixustat | small molecules | FDA | 2017-01-04 | — | Acucela Inc. |
ABCA4 DNA nanoparticles | oligonucleotides | FDA | 2015-10-28 | — | Copernicus Therapeutics, Inc. |
Ecothiopate iodide | small molecules | EMA | 2015-04-24 | — | Dorian Regulatory Affairs B.V. |
Mixture of two adeno-associated viral vectors of serotype 8 containing the 5'-half sequence of human ABCA4 gene and the 3'-half sequence of human ABCA4 gene | gene therapies | EMA | 2014-07-04 | — | Fondazione Telethon Ets |
echothiophate iodide | small molecules | FDA | 2014-06-02 | — | Makindus, Inc. |
Soraprazan | small molecules | EMA | 2013-11-13 | — | Katairo GmbH |
Ramiprilat | small molecules | EMA | 2013-03-12 | — | Yes Pharmaceutical Development Services GmbH |
Envuretcel | cell therapies | EMA | 2011-06-21 | — | Astellas Pharma Europe B.V. |
C20-D3-retinyl acetate | small molecules | FDA | 2010-09-16 | — | Alkeus pharmaceuticals, Inc. |
lentiviral vector containing the human ABCA4 gene | gene therapies | FDA | 2010-04-30 | — | Sanofi US Services Inc. |
Lentiviral vector containing the human ABCA4 gene | gene therapies | EMA | 2010-02-02 | — | Sanofi Winthrop Industrie |
MA09-hRPE cells | cell therapies | FDA | 2010-02-02 | — | Astellas Pharma Global Development Inc. |
Adeno-associated viral vector serotype 5 containing the human ABCA4 gene | gene therapies | EMA | 2009-02-06 | — | Fondazione Telethon Ets |
Adeno-associated viral vector serotype 5 containing human ABCA4 gene | gene therapies | FDA | 2008-09-30 | — | Fondazione Telethon |