Drug discovery
17
drugs
With orphan designations
Overview
Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscle disorder characterized by progressive weakness in facial, shoulder, and upper arm muscles, often spreading to other muscle groups. Caused by misexpression of the DUX4 gene due to genetic/epigenetic dysregulation, it typically manifests in adolescence or adulthood (rarely in infancy) with variable severity. Extramuscular features include hearing loss (≤30% in childhood cases), retinal vascular abnormalities, and chronic pain. Respiratory/cardiac involvement is rare but possible in severe cases [1][5][6][11].
Burden
Economic: Annual per-patient costs exceed $28,000 (U.S.) and €26,322 (EU), driven by home care, assistive devices, and lost productivity [4][9].
Morbidity: 20% require wheelchairs by age 50; chronic pain affects >75% of patients [1][16].
Quality of life: Median health utility scores (0.63) reflect significant impairment vs. general populations [9][16].
Therapies
Symptomatic management: Physical therapy, scapular fixation surgery, pain management, and low-intensity aerobic exercise [1][6][11].
Emerging therapies: DUX4-targeted approaches (e.g., losmapimod [p38 inhibitor], CRISPR, antisense oligonucleotides) [3][13][18].
Trials: Anti-inflammatory/antioxidant agents (e.g., FLAVOMEGA, β2-agonists) show modest functional improvements [8][10].
Categories: rare genetic diseases, rare neurological diseases
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
double homeobox 4 -anti-sense oligonucleotide | oligonucleotides | FDA | 2026-02-02 | — | Solve FSHD |
small molecule inhibitor of the DUX4 transcription factor | small molecules | FDA | 2025-11-19 | — | Altay Therapeutics |
AAV-based gene therapy expressing artificial microRNA targeting the human DUX4 open reading frame | gene therapies | FDA | 2024-10-16 | — | Armatus Bio |
Adeno-Associated Viral Vector Expressing Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/dCas-based Gene Therapy consisting of a Single Guide RNA targeting the Human D4Z4 Locus and a messenger RNA encoding dCasONYX | gene therapies | FDA | 2023-11-14 | — | EpiCrispr Biotechnologies, Inc. |
Humanised IgG1 monoclonal antibody against TfR1 conjugated to double stranded siRNA oligonucleotide against DUX4 mRNA via a non-cleavable linker | combination | EMA | 2023-02-15 | — | MWB Consulting |
An antibody oligonucleotide conjugate, comprised of a human transferrin receptor 1 targeting, effector function null, humanized IgG1 antibody, a MCC maleimide linker, and a double-stranded siRNA oligonucleotide targeting DUX4 | oligonucleotides | FDA | 2023-02-13 | — | Avidity Biosciences, Inc. |
nandrolone | small molecules | FDA | 2022-01-06 | — | Sarcomed AB |
Losmapimod | small molecules | EMA | 2020-03-24 | — | Sanofi B.V. |
losmapimod | small molecules | FDA | 2020-01-27 | — | Fulcrum Therapeutics, Inc. |
Follistatin291-IgG2 Fc fusion protein | proteins | FDA | 2018-07-03 | — | Acceleron Pharma Inc. |
rebastinib | small molecules | FDA | 2018-05-23 | — | Genea Biocells US Inc. |
Ascorbic acid | small molecules | EMA | 2016-11-18 | — | Université de Montpellier |
Zinc gluconate | small molecules | EMA | 2016-11-18 | — | Université de Montpellier |
L-selenomethionine | small molecules | EMA | 2016-11-18 | — | Université de Montpellier |
Alpha-tocopherol | small molecules | EMA | 2016-11-18 | — | Université de Montpellier |
recombinant human histidyl tRNA synthetase | proteins | FDA | 2015-04-22 | — | aTyr Pharma, Inc. |
Amino acids 2-506 of the wild-type human histidyl-tRNA synthetase [ATYR1940] | proteins | EMA | 2015-02-12 | — | Voisin Consulting Life Sciences |