Drug discovery
77
drugs
With orphan designations
Overview
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene, leading to progressive motor dysfunction (e.g., chorea, rigidity), cognitive decline, and psychiatric symptoms. Onset typically occurs in mid-adulthood (30–50 years), with juvenile forms (<20 years) presenting severe parkinsonism. Diagnosis is confirmed by genetic testing. While incurable, symptom management includes pharmacotherapy, multidisciplinary care, and emerging disease-modifying therapies targeting mutant huntingtin protein (mHTT) reduction [1][5][9][13].
Burden
Life expectancy: 10–30 years post-onset; juvenile HD progresses faster [9][13].
High morbidity: Loss of independence, dysphagia, dementia, and suicide rates 4–8× higher than general population [9][13][16].
Economic/psychosocial strain: Full-time care required in advanced stages; significant caregiver burden [17][20].
Therapies
Symptomatic control: Chorea managed with VMAT2 inhibitors (tetrabenazine, deutetrabenazine), antipsychotics (olanzapine), and anti-glutamatergics (amantadine, riluzole) [3][9][19].
Supportive care: Physical/occupational therapy, psychiatric interventions, and caregiver support [1][17].
Emerging therapies: Antisense oligonucleotides (ASOs, e.g., RG6042 in Phase 3), RNA interference, and CRISPR-based gene editing to reduce mHTT [7][11][15].
Categories: rare genetic diseases, rare neurological diseases, rare ophthalmic disorders
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
sulphamic acid, 6,7,8,9,10,11-hexahydro-6-oxobenzo[b]cyclohepta[d]pyran-3-yl ester | small molecules | FDA | 2026-03-16 | — | Olavide Neuron STX S.L. |
a small molecule agonist of TrkB receptor | small molecules | FDA | 2026-03-12 | — | Shaanxi Micot Technology Co., Ltd. |
tiapride | small molecules | FDA | 2025-10-22 | — | ArKri Therapeutics |
Bevantolol hydrochloride | small molecules | EMA | 2025-10-22 | — | Som Innovation Biotech S.A. |
monosialotetrahexosylganglioside sodium salt of porcine brain origin (pGM1) | other | FDA | 2025-10-16 | — | Zulia Biotech Inc. |
Votoplam | small molecules | EMA | 2024-12-13 | — | Novartis Europharm Limited |
2'-O-(2-methoxyethyl) and 2¿-O-methyl modified antisense oligonucleotide targeted to mutant huntingtin RNA | oligonucleotides | FDA | 2024-11-07 | — | Wave Life Sciences USA, Inc. |
votoplam | small molecules | FDA | 2024-10-25 | — | Novartis Pharmaceuticals Corporation |
(3beta,24S)-25,25,25-trifluoro-3-methyl-26,27-dinorergost-5-ene-3,24-diol | small molecules | FDA | 2023-10-16 | — | Sage Therapeutics |
Virus-like particle containing Cas9/gRNA ribonucleoprotein targeting the human HTT gene | gene therapies | FDA | 2023-10-05 | — | Shanghai BDgene Co., Ltd. |
Virus-like particle containing Cas9/gRNA ribonucleoprotein targeting the human HTT gene | gene editing enzymes | EMA | 2023-08-16 | — | Laura Nae |
A plasmid encoding a rabies virus glycoprotein tag & lysosome-associated membrane glycoprotein 2 fusion protein gene and a mutant huntingtin small interfering RNA | combination | FDA | 2023-04-10 | — | ExoRNA Bioscience Nanjing Co. Ltd. |
Dalzanemdor | small molecules | EMA | 2023-02-15 | — | Raremoon Consulting Esp S.L. |
valbenazine [Ingrezza] | small molecules | FDA | 2022-05-10 | 2023-08-18 | Neurocrine Biosciences Inc. |
synthetic 23 amino acid peptide AASSGVSTPGSAGHDIITEQPRS derived from the Huntingtin protein | peptides | FDA | 2021-11-04 | — | centre national de la recherche scientifique |
humanized recombinant immunoglobulin G (IgG) 4 monoclonal antibody against C1q | antibodies | FDA | 2021-10-25 | — | Annexon, Inc. |
an antisense oligonucleotide that has been developed to target expanded CAG repeats in messenger ribonucleic acid (mRNA) | oligonucleotides | FDA | 2021-07-27 | — | Vico Therapeutics B.V. |
Bevantolol Hydrochloride (HCl) | small molecules | FDA | 2021-06-24 | — | SOM Innovation Biotech S.A. |
Branaplam | small molecules | FDA | 2020-10-19 | — | Novartis Pharmaceuticals Corporation |
fasudil HCL | small molecules | FDA | 2020-08-25 | — | Woolsey Pharmaceuticals, Inc. |
Umbilical Cord Mesenchymal Stem Cells | cell therapies | FDA | 2020-01-28 | — | Acen Regenerative Medicine Sci-Tech Co., Ltd. |
2-(3,7-dimethyl-octa-2, 6-dienyl)-6-ethylamino-3-hydroxy-5-pentyl-[1,4]benzoquinone | small molecules | EMA | 2020-01-09 | — | Emerald Health Pharmaceuticals España, S.L. |
vasopressin 1a receptor antagonist | small molecules | FDA | 2019-10-30 | — | Azevan Pharmaceuticals, Inc. |
glycerol tribenzoate | small molecules | FDA | 2019-09-10 | — | Forest Hills Partners Hong Kong Limited |
(1E,6E)-1,7-Bis(3,4-dimethoxyphenyl)-4-cyclobutylmethyl-1,6-heptadiene-3,5-dione OR [(1E,4Z,6E)-4-(cyclobutylmethyl)-1,7-bis(3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one] | small molecules | FDA | 2019-05-14 | — | AnnJi Pharmaceutical Co. Ltd. |
ADENO-ASSOCIATED VIRAL VECTOR SEROTYPE RH10 CONTAINING THE HUMAN CHOLESTEROL 24-HYDROXYLASE GENE | gene therapies | EMA | 2019-04-01 | — | AskBio France |
recombinant adeno-associated virus, serotype 1, containing a transgene that encodes a microRNA targeting huntingtin messenger RNA | gene therapies | FDA | 2019-03-15 | — | Voyager Therapeutics |
2,4-dinitrophenol | small molecules | FDA | 2019-02-11 | — | Mitochon Pharmaceuticals, Inc. |
delta-9-tetrahydrocannabinol and cannabidiol | small molecules | FDA | 2019-01-29 | — | MMJ International Holdings |
(+)-alpha-dihydrotetrabenazine | small molecules | FDA | 2018-12-05 | — | Adeptio Pharmaceuticals, Ltd |
recombinant adeno-associated virus vector containing DNA encoding INT41 intrabody | gene therapies | FDA | 2018-11-30 | — | Vybion Inc. |
monosialotetrahexosylganglioside | small molecules | FDA | 2018-08-07 | — | Qilu Pharmaceutical Co., Ltd. |
2-(3,7-Dimethyl-octa-2, 6-dienyl)¿6-ethylamino-3-hydroxy-5-pentyl-[1,4]benzoquinone | small molecules | FDA | 2018-02-01 | — | Emerald Health Pharmaceuticals Inc. |
Adeno-associated viral vector serotype 5 encoding a microRNA targeted to human huntingtin gene | gene therapies | EMA | 2018-01-17 | — | uniQure Biopharma B.V. |
adeno-associated viral vector serotype 5 encoding a microRNA targeted to human huntingtin gene | gene therapies | FDA | 2017-09-27 | — | uniQure Biopharma B.V. |
synthetic stereopure antisense oligonucleotide specific to the mutant huntingtin mRNA transcript at the U variant of single nucleotide polymorphism rs326331 | oligonucleotides | FDA | 2017-09-05 | — | Wave Life Sciences Ltd. |
laquinimod sodium | small molecules | FDA | 2017-01-31 | — | Active Biotech AB |
Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Gly-Gly-Asp-Leu-Leu-Pro-Arg-Gly-Ser | peptides | EMA | 2016-11-18 | — | Granzer Regulatory Consulting & Services GmbH |
humanized IgG4 monoclonal antibody that binds to the SEMA4D antigen | antibodies | FDA | 2016-08-16 | — | Vaccinex, Inc. |
Mardepodect [PF-02545920] | small molecules | EMA | 2016-07-14 | — | Pfizer Limited |
antisense oligonucleotide targeting the U isoform of SNP rs362307 | oligonucleotides | FDA | 2016-06-16 | — | Wave LIfe Sciences |
Tominersen | oligonucleotides | FDA | 2015-12-29 | — | Genentech, Inc. |
5,7-dichloro-2-dimethylaminomethyl-8-hydroxyquinoline | small molecules | EMA | 2015-05-21 | — | [INACTIVE] Veristat Spain S.L. |
AASSGVSTPGSAGHDIITEQPRS | peptides | EMA | 2015-05-21 | — | Centre National de la Recherche Scientifique (CNRS) |
4-[2-(aminomethyl)-1,3-thiazol-4-yl]-2,6-ditert-butylphenol hydrochloride [BN82451B] | small molecules | EMA | 2015-04-24 | — | Ipsen Pharma |
Chimeric 2'-O-(2-methoxyethyl) modified oligonucleotide targeted to huntingtin RNA | oligonucleotides | EMA | 2015-03-19 | — | Roche Registration GmbH |
phenol, 4-[2-(aminomethyl)-4-thiazolyl]-2,6-bis (1,1-dimethyethyl) monohydrochloride | small molecules | FDA | 2015-03-16 | — | Ipsen Biopharmaceuticals, Inc. |
2'-O-methyl phosphorothioate RNA oligonucleotide, 5'-m5CUGm5CUGm5CUGm5CUGm5CUGm5CUGm5CUG-3' | oligonucleotides | EMA | 2015-02-18 | — | Vico Therapeutics B.V. |
5-bromo-N-(prop-2-yn-1-yl)-2-(1H-1,2,4-triazol-1-yl)pyrimidine-4,6-diamine | small molecules | EMA | 2014-12-16 | — | Palobiofarma S.L. |
d6-tetrabenazine, deutetrabenazine [Austedo] | small molecules | FDA | 2014-11-05 | 2017-04-03 | Teva Branded Pharmaceutical Products R&D, Inc. |
5,7-dichloro-2-dimethylaminomethyl-8-hydroxyquinoline hydrochloride | small molecules | FDA | 2014-09-04 | — | Prana Biotechnology Limited |
Cysteamine bitartrate | small molecules | EMA | 2014-07-29 | — | Chiesi Farmaceutici S.p.A. |
carbenoxolone | small molecules | FDA | 2014-07-02 | — | Oxalys Pharmaceuticals, Inc. |
2-[4-(1-Methyl-4-pyridin-4-yl-lH-pyrazol-3-yl)-phenoxymethyl]-quinoline succinic acid | small molecules | FDA | 2014-06-02 | — | Pfizer Inc. |
small molecule inhibitor of phosphodiesterase 10 | small molecules | FDA | 2013-09-26 | — | Omeros Corporation |
lithium citrate tetrahydrate (in reverse micelle formulation) | small molecules | FDA | 2010-12-13 | — | Medesis Pharma |
Lithium citrate tetrahydrate (in reverse-micelle formulation) | small molecules | EMA | 2010-01-28 | — | Medesis Pharma |
selisistat | small molecules | FDA | 2009-12-07 | — | AOP Orphan Pharmaceuticals AG |
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide | small molecules | EMA | 2009-10-28 | — | Aop Orphan Pharmaceuticals GmbH |
recombinant adeno-associated virus encoded gene for X-linked mammalian inhibitor of apoptosis protein (XIAP) | gene therapies | FDA | 2009-08-25 | — | Neurologix, Inc. |
dimebon | small molecules | FDA | 2009-05-12 | — | Medivation, Inc. |
Latrepirdine dihydrochloride | small molecules | EMA | 2009-01-20 | — | IDEA Innovative Drug European Associates Limited |
cysteamine | small molecules | FDA | 2008-05-09 | — | Horizon Therapeutics USA, Inc. |
Clotrimazole | small molecules | FDA | 2006-03-13 | — | EnVivo Pharmaceuticals, Inc. |
4-(3-Methanesulfonyl-phenyl)-1-propylpiperidine HCl | small molecules | FDA | 2005-12-12 | — | Prilenia Therapeutics |
Creatine | small molecules | FDA | 2005-10-11 | — | Marathon Pharmaceuticals, LLC |
4-[3-(methylsulfonyl)phenyl]-1-propylpiperidine x HCl | small molecules | EMA | 2005-06-20 | — | Ferrer Internacional S.A. |
ubiquinol | small molecules | FDA | 2004-04-12 | — | Gel-Tec, Division of Tishcon Corp. |
Coenzyme Q10 | small molecules | FDA | 2001-03-05 | — | Integrative Therapeutics, Inc. |
Ethyl Eicosopentaenoate | small molecules | EMA | 2000-12-29 | — | Amarin Neuroscience Limited |
Ethyl eicosapentaenoate | small molecules | FDA | 2000-04-06 | — | Laxdale Ltd. |
Remacemide | small molecules | FDA | 2000-03-06 | — | AstraZeneca LP |
Tiapride | — | FDA | 1998-04-21 | — | Sanofi-Synthelabo, Inc. |
Tetrabenazine [Xenazine] | small molecules | FDA | 1997-12-11 | 2008-08-15 | Prestwick Pharmaceuticals, Inc |
Porcine fetal neural gabaergic cells and/or precursors aseptically prepared and coated with anti-MHC-1 Ab for intracerebral implantation | cell therapies | FDA | 1996-12-10 | — | Diacrin/Genzyme LLC |
Porcine fetal neural gabaergic cells and/or precursors aseptically prepared for intracerebral implantation for Huntington's disease. | cell therapies | FDA | 1996-12-10 | — | Diacrin/Genzyme LLC |
Riluzole | small molecules | FDA | 1996-10-15 | — | Rhone-Poulenc Rorer Pharmaceuticals, Inc. |