HDAC Inhibitors
3 drugsAbout HDAC
Histone deacetylases (HDACs) are enzymes that regulate gene expression by removing acetyl groups from histone proteins, leading to chromatin condensation and transcriptional repression. They influence various cellular processes, making them attractive targets for therapeutic intervention.
Genetic evidence offers moderate support for HDAC1 as a therapeutic target, with variants linked to genetic disorders (score 0.44). Colocalization studies show strong eQTL/pQTL signals, further supporting its role in disease.
Three FDA-approved small molecule drugs target HDACs, including ISTODAX, ROMIDEPSIN, and BELEODAQ, all approved for other therapeutic areas. Bristol-Myers Squibb, Fresenius Kabi, and ACROTECH BIOPHARMA are the key players in this space.
HDAC Genetic Evidence Moderate
Genetic evidence provides moderate support for HDAC1, with a max score of 0.44 linked to genetic disorders.
Further investigation of HDAC1's role in genetic disorders may reveal novel therapeutic strategies.
Evidence Across Diseases
1 totalGWAS and other genetic studies link HDAC1 to 1 diseases.
🔗 Colocalization Evidence 1 strong
max H4: 1.00eQTL/pQTL signals for HDAC1 colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top HDAC Drugs
Bristol-Myers Squibb, Fresenius Kabi, and ACROTECH BIOPHARMA are the only companies with approved HDAC-targeting drugs.
The limited number of players suggests relatively low barriers to entry for new HDAC-targeting therapies.
HDAC Drug Modality Landscape
Modalities
Routes of Administration
HDAC is druggable by small molecules, though no oral formulations are currently approved.
Exploring alternative modalities like PROTACs or biologics could offer a competitive advantage.
HDAC Clinical Trials 92 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on HDAC. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 68 | 40 | 23 | 5 | 63% |
| Phase 2 | 17 | 12 | 1 | 4 | 92% |
| Phase 3 | 7 | 4 | 1 | 2 | 80% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved HDAC drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting HDAC. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
HDAC Drug Approval Timeline (2009 - 2014)
The first HDAC-targeting drug was approved in 2009 (ISTODAX), with the most recent approval in 2020 (ROMIDEPSIN).
The recent approval suggests continued interest, but the slow pace indicates potential challenges in development.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 3 companies competing
- • Market share by company
Full Drug Portfolio
- • All 3 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 3-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 49 (8 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on HDAC. A trial counts if an approved drug acting on HDAC is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.