Drug discovery
18
drugs
With orphan designations
Overview
Osteogenesis imperfecta (OI) is a genetic disorder caused by defective collagen production or processing, leading to bone fragility, recurrent fractures, and systemic manifestations like blue sclerae, dentinogenesis imperfecta, hearing loss, and joint hypermobility. Severity ranges from mild (Type I) to perinatal lethality (Type II), with autosomal dominant COL1A1/2 mutations accounting for 90% of cases [1][2][7]. Diagnosis combines clinical evaluation, imaging, and genetic testing [6][14].
Burden
Hospitalization rates are 2.9× higher than the general population, peaking in ages 0–19 (8.4×) [4][9]. Mortality risks include respiratory insufficiency (severe OI) and cardiovascular complications (moderate/mild OI) [4][9]. Families report significant financial strain (29.6% spending >10% income on OI-related costs) [19].
Therapies
Pharmacologic: Bisphosphonates (e.g., zoledronate) to reduce fracture risk [5][13][18]; emerging therapies include anti-RANKL agents (denosumab) and TGF-β inhibitors [18].
Surgical/Rehabilitative: Intramedullary rodding for long-bone stabilization [5][13]; physiotherapy to enhance mobility and prevent deconditioning [3][8][16].
Multidisciplinary care: Dental interventions, hearing aids, and cardiopulmonary monitoring [5][6][14].
Categories: rare bone diseases, rare developmental anomalies during embryogenesis, rare genetic diseases
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
N-[(2S)-1-[(3aS,6R,6aR)-6-Ethynyl-3-oxohexahydro-2H-furo[3,2-b]pyrrol-4-yl]-4-methyl-1-oxopentan-2-yl]-4-[5-fluoro-2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]benzamide hydrochloride | small molecules | FDA | 2025-11-25 | — | OsteoCat Therapeutics AB |
Humanised IgG4 bispecific monoclonal antibody against sclerostin and dickkopf-related protein 1 | antibodies | EMA | 2025-06-20 | — | Worldwide Clinical Trials |
anti-Siglec-15 monoclonal antibody on a human IgG1-Fc-silenced backbone | antibodies | FDA | 2024-05-29 | — | NextCure, Inc. |
DNA, (Cm-Gm-Gm-Gm-G-T-G-T-G-G-G-T-T-C-G-T-C-G-T-T-A-G-C-T-T-G-A-T-T-T-G-G-C-A-G-C-Um-Gm-Cm-Cm-(5'->3')-dT), 5'-ester with (29S)-29-(tert-butoxycarbonyl)-1-((hydroxyphosphoryl)oxy)-8,17,26,31-tetraoxo-10,13,19,22-tetraoxa-7,16,25,30-tetraazaoctatetracontan-48-oic acid | oligonucleotides | FDA | 2022-11-03 | — | Aptacure Therapeutics Limited |
A Humanized Bispecific Antibody Neutralizing Both Sclerostin and Dickkopf-1 | antibodies | FDA | 2022-10-20 | — | Angitia Biopharmaceuticals Guangzhou Limited |
anti-human transforming growth factor beta (TGF-Beta) monoclonal antibody (mAb), based on the amino acid sequence of the human monoclonal antibody fresolimumab (GC1008) with the exception of one serine to proline substitution | antibodies | FDA | 2022-10-15 | — | Sanofi Genzyme, A Sanofi Company |
Losartan | small molecules | EMA | 2022-06-21 | — | 3R Pharma Consulting GmbH |
allogenic fetal mesenchymal stem cells | cell therapies | FDA | 2022-05-06 | — | BOOST Pharma Aps |
Allogeneic fetal mesenchymal stem cells | cell therapies | EMA | 2021-12-10 | — | Boost Pharma ApS |
romosozumab | antibodies | FDA | 2021-05-10 | — | Amgen Inc. |
denosumab | antibodies | FDA | 2021-02-02 | — | Amgen Inc. |
DNA, (Cm-Gm-Gm-Gm-G-T-G-T-G-G-G-T-T-C-G-T-C-G-T-T-A-G-C-T-T-G-A-T-T-T-G-G-C-A-G-C-Um-Gm-Cm-Cm-(3'¿3')-dT), 5'-ester with [[5-(phosphoonoxy) pentyl] amino] carbonyl-oxy-1, 2-ethanediyl, sodium salt | oligonucleotides | FDA | 2019-08-19 | — | Aptacure Therapeutics Limited |
Recombinant humanised monoclonal IgG2 lambda antibody against human sclerostin | antibodies | EMA | 2016-06-27 | — | Mereo BioPharma Europe B.V. |
human monoclonal antibody targeting human sclerostin | antibodies | FDA | 2016-02-29 | — | Ultragenyx Pharmaceutical, Inc. |
human allogeneic bone marrow derived osteoblastic cells | cell therapies | FDA | 2015-11-09 | — | Biosenic SA |
Human allogeneic bone-marrow-derived osteoblastic cells | cell therapies | EMA | 2015-08-10 | — | BioSenic |
risedronate sodium | small molecules | FDA | 2006-12-18 | — | Warner Chilcott Pharmaceuticals |
alendronate | small molecules | FDA | 2003-03-31 | — | Merck, Sharpe & Dohme Corp. |