ALK Inhibitors
7 drugsAbout ALK
Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase involved in cell growth and differentiation. It is activated by ligand binding, leading to downstream signaling cascades that promote cell survival and proliferation.
ALK is strongly validated as a therapeutic target by human genetics, with a max score of 0.97 linking it to neuroblastoma. Gain-of-function mutations are associated with increased disease risk, suggesting that inhibition is likely beneficial.
ALK is targeted by 7 FDA-approved small molecule drugs, including XALKORI, ROZLYTREK, and ALUNBRIG, primarily in oncology. The first drug was approved in 2011, with the most recent approval in 2024.
ALK Genetic Evidence Strong
ALK has strong genetic support with a score of 0.97, linking it to neuroblastoma.
Strong genetic support suggests a higher probability of clinical trial success for ALK-targeting therapies.
💡 Why inhibition?
- • Gain-of-function variants increase disease risk — blocking overactivity may help
- • 100% directional consistency across 1 traits
- • Strong signal in nervous system disease, cancer or benign tumor pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
15 totalGWAS and other genetic studies link ALK to 15 diseases.
Gain-of-function causes disease; inhibition may help
🔗 Colocalization Evidence 1 strong
max H4: 0.99eQTL/pQTL signals for ALK 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 ALK Drugs
Six companies have approved ALK-targeting drugs, including Roche, Takeda, and Novartis.
The presence of multiple established players indicates a moderately competitive market with potential entry barriers.
ALK Drug Modality Landscape
Modalities
Routes of Administration
ALK is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or PROTACs could provide a competitive advantage.
ALK Clinical Trials 244 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on ALK. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 95 | 57 | 17 | 21 | 77% |
| Phase 2 | 108 | 30 | 23 | 55 | 57% |
| Phase 3 | 29 | 11 | 0 | 18 | 100% |
| Phase 4 | 12 | 2 | 2 | 8 | 50% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
4 Phase 3 trials testing approved ALK drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting ALK. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
ALK Drug Approval Timeline (2011 - 2024)
ALK has seen approvals spanning 14 years, from 2011 to 2024.
The continued approvals suggest sustained interest and potential for further development in ALK-targeted therapies.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 6 companies competing
- • Market share by company
Full Drug Portfolio
- • All 7 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 7-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 106 (22 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 ALK. A trial counts if an approved drug acting on ALK 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.