Drug discovery
36
drugs
With orphan designations
Overview
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by GAA repeat expansions in the FXN gene, leading to frataxin deficiency. It features progressive ataxia, dysarthria, sensory loss, hypertrophic cardiomyopathy (60–75% of cases), scoliosis, and diabetes (20–30%). Onset typically occurs in childhood/adolescence, with wheelchair dependence within 10–20 years. Multisystem involvement necessitates multidisciplinary care. Mortality averages 36–37 years, often due to cardiac complications [1][6][14][16].
Burden
Morbidity: 95% require wheelchairs by age 45; 32% non-ambulatory by adulthood [4][14].
Mortality: Median age of death 36.5 years; cardiac complications (62%) are the leading cause [2][5][14].
Economic impact: Annual US healthcare costs exceed $18,000/patient (adjusted), with 6x higher home health needs vs. controls [4][5][14].
Therapies
Symptomatic management: Physical/occupational therapy, botulinum toxin for spasticity, beta-blockers/ACE inhibitors for cardiomyopathy [3][6][15].
Disease-modifying: Omaveloxolone (Skyclarys®), the first FDA-approved therapy, reduces oxidative stress and slows progression [8][17].
Emerging approaches: Gene therapy, frataxin replacement, and epigenetic modifiers in clinical trials [13][18][19].
Categories: rare cardiac diseases, rare genetic diseases, rare neurological diseases, rare ophthalmic disorders, rare transplant-related disorders
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
recombinant adeno-associated virus (AAV) vector encoding the human frataxin (hFXN) gene | gene therapies | FDA | 2026-05-07 | — | Neurocrine Biosciences, Inc. |
recombinant non-replicating adeno-associated virus serotype hu68 containing a codon-optimized cDNA that encodes the consensus sequence of the human frataxin protein | gene therapies | FDA | 2025-12-04 | — | Solid Biosciences Inc. |
recombinant adeno-associated virus serotype 8 expressing codon optimized human frataxin gene cDNA under the control of a ubiquitous hPGK promoter (rAAV8-hPGK-hFXNco) | gene therapies | FDA | 2024-09-24 | — | Astellas Gene Therapies, Inc. |
autologous human CD34+ hematopoietic stem and progenitor cells isolated from mobilized peripheral blood stem cell of patients with Friedreich's ataxia, modified ex vivo using CRISPR/Cas9 technology to remove the GAA hyper-expansion mutation in the intron 1 of frataxin | gene editing enzymes | FDA | 2024-07-30 | — | Papillon Therapeutics Inc. |
Adeno-associated virus vector serotype rh.10 containing the human FXN gene | gene therapies | EMA | 2024-07-25 | — | Scendea (NL) B.V. |
elamipretide | peptides | FDA | 2022-03-22 | — | Stealth Biotherapeutics, Inc. |
Adeno-associated viral vector encoding the human frataxin (FXN) gene, AAVrh.10hFXN | gene therapies | FDA | 2021-06-24 | — | Lexeo Therapeutics |
Zaftuclenegene piruparvovec | gene therapies | EMA | 2021-06-21 | — | [INACTIVE] Novartis Gene Therapies EU Limited |
Vatiquinone | small molecules | EMA | 2021-03-26 | — | PTC Therapeutics International Limited |
AAV9 gene vector construct expressing the human Frataxin gene (scAAV9.CB.hFRXN isoform 1) | gene therapies | FDA | 2021-01-21 | — | Novartis Institute for BioMedical Research, Inc. |
Human frataxin fused to TAT cell-penetrating peptide | proteins | EMA | 2020-08-21 | — | Yes Pharmaceutical Development Services GmbH |
Leriglitazone | small molecules | EMA | 2019-10-17 | — | Minoryx Therapeutics S.L. |
leriglitazone | small molecules | FDA | 2019-08-01 | — | Minoryx Therapeutics S.L. |
Luvadaxistat | small molecules | EMA | 2019-04-01 | — | Takeda Pharma A/S |
Omaveloxolone [Skyclarys] | small molecules | EMA | 2018-06-27 | 2024-02-12 | Biogen Netherlands B.V. |
Dimethyl fumarate | small molecules | EMA | 2018-03-21 | — | Qualix Pharma S.L. |
D-amino acid oxidase inhibitor | small molecules | FDA | 2017-12-06 | — | Takeda Development Center Americas, Inc. |
Recombinant adeno-associated viral vector serotype 5 carrying the gene for the human frataxin protein | gene therapies | EMA | 2017-08-23 | — | PTC Therapeutics International Limited |
trans-resveratrol | small molecules | FDA | 2017-08-16 | — | Jupiter Orphan Therapeutics |
Fusion protein linking human frataxin to a cell-penetrant peptide | proteins | FDA | 2017-07-19 | — | Larimar Therapeutics, Inc. |
omaveloxolone [Skyclarys] | small molecules | FDA | 2017-06-19 | 2023-02-28 | Biogen U.S. Corporation |
recombinant, adeno-associated virus serotype 5 vector, containing the transgene, which encodes for the human protein, frataxin | gene therapies | FDA | 2016-07-25 | — | PTC Therapeutics, Inc. |
9-cis, 12-cis-11,11-d2-linoleic acid ethyl ester | small molecules | FDA | 2016-05-23 | — | Retrotope, Inc. |
interferon gamma-1b | proteins | FDA | 2014-10-01 | — | Horizon Therapeutic Ireland DAC |
vatiquinone | small molecules | FDA | 2014-01-31 | — | PTC Therapeutics, Inc. |
dimethyl fumarate | small molecules | FDA | 2013-09-11 | — | Ixchel Pharma, LLC |
Interferon gamma | proteins | EMA | 2011-12-09 | — | Horizon Therapeutics Ireland Designated Activity Company |
interferon gamma | proteins | FDA | 2011-11-04 | — | Roberto Testi, MD |
coenzyme Q10 and d-alpha-tocopherol | small molecules | FDA | 2011-03-14 | — | NBI Pharmaceuticals, Inc. |
N-(6-(2-aminophenylamino)-6-oxohexyl)-4-methylbenzamide | small molecules | EMA | 2010-10-01 | — | Repligen Europe Limited |
N-(6-2-aminophenylamino)-6-oxohexyl)-4-methylbenzamide | small molecules | FDA | 2010-05-17 | — | Repligen Corporation |
deferiprone | small molecules | FDA | 2008-07-31 | — | Chiesi USA, Inc. |
idebenone | small molecules | FDA | 2004-03-25 | — | Chiesi Farmaceutici S.p.A. |
Idebenone | small molecules | EMA | 2004-03-08 | — | Chiesi Farmaceutici S.p.A. |
Idebenone | small molecules | EMA | 2001-11-20 | — | Laboratoires Takeda |
physostigmine salicylatephysostigmine salicylate | small molecules | FDA | 1985-01-16 | — | Forest Pharmaceuticals.3-.3-.30 6 |