Across 55 unique European CTIS-authorized Phase II & III myelodysplastic syndrome trials, safety and tolerability dominated endpoint design, appearing in 48 trials (87.3%). The next most frequent endpoint families were clinical response/remission in 33 trials (60.0%), overall survival in 32 trials (58.2%), and progression to AML or higher-risk MDS in 30 trials (54.5%). Primary endpoints were more safety- and response-led, while secondary endpoints carried most survival, MRD, biomarker, quality-of-life, and duration measures.
Safety / tolerability endpoints appeared in 48 of 55 trials (87.3%). Response/remission endpoints appeared in 33 trials (60.0%), overall survival (OS) in 32 trials (58.2%), progression to acute myeloid leukemia (AML) or higher-risk MDS in 30 trials (54.5%), and transfusion independence or transfusion burden in 24 trials (43.6%).
European MDS endpoint design is not built around one efficacy measure. Safety is near-universal, while efficacy splits into AML-risk control, remission depth, survival, transfusion benefit, and transplant-related outcomes.
Safety / tolerability was a primary endpoint family in 27 trials (49.1%) and secondary in 39 trials (70.9%). Clinical response/remission was primary in 19 trials (34.5%) and secondary in 27 trials (49.1%). OS was rarely primary at 6 trials (10.9%) but common as secondary at 31 trials (56.4%). Exploratory/other endpoint fields were populated in 0 of 55 trials (0.0%).
| Endpoint family | Primary | Secondary | Other |
|---|---|---|---|
| Safety / tolerability | 27 / 55 | 39 / 55 | 0 / 55 |
| Clinical response / remission | 19 / 55 | 27 / 55 | 0 / 55 |
| Progression to AML / higher-risk MDS | 11 / 55 | 26 / 55 | 0 / 55 |
| Transfusion independence / burden | 10 / 55 | 21 / 55 | 0 / 55 |
| Overall survival | 6 / 55 | 31 / 55 | 0 / 55 |
| Event-free survival | 5 / 55 | 14 / 55 | 0 / 55 |
| Biomarker / pharmacodynamic | 3 / 55 | 16 / 55 | 0 / 55 |
| Quality of life / PRO | 0 / 55 | 14 / 55 | 0 / 55 |
For EU MDS submissions, primary endpoint strategy is usually designed around tolerability, response, or disease progression. Secondary endpoint packages are much broader and are where OS, MRD, PRO, biomarker, and duration measures most often appear.
Among 40 Phase II trial-phase records, safety appeared in 38 (95.0%), response/remission in 28 (70.0%), OS in 25 (62.5%), and AML/higher-risk progression in 25 (62.5%). Among 18 Phase III trial-phase records, safety appeared in 13 (72.2%), OS in 10 (55.6%), and transfusion independence/burden in 9 (50.0%).
| Endpoint family | Phase II | Phase III |
|---|---|---|
| Safety / tolerability | 38 / 40 · 95.0% | 13 / 18 · 72.2% |
| Clinical response / remission | 28 / 40 · 70.0% | 8 / 18 · 44.4% |
| Overall survival | 25 / 40 · 62.5% | 10 / 18 · 55.6% |
| Progression to AML / higher-risk MDS | 25 / 40 · 62.5% | 7 / 18 · 38.9% |
| Transfusion independence / burden | 17 / 40 · 42.5% | 9 / 18 · 50.0% |
| Biomarker / pharmacodynamic | 13 / 40 · 32.5% | 6 / 18 · 33.3% |
| Relapse / relapse-free outcomes | 12 / 40 · 30.0% | 6 / 18 · 33.3% |
Phase II CTIS submissions are more exploratory in clinical logic, with heavier safety, response, and progression coverage. Phase III designs shift toward confirmatory benefit endpoints, especially transfusion independence and survival.
AML/MDS-AML overlap appeared in 33 of 55 trials (60.0%), higher-risk or excess-blast MDS in 16 trials (29.1%), lower-risk/anemia/transfusion-dependent MDS in 11 trials (20.0%), and MDS/MPN or CMML overlap in 10 trials (18.2%). In lower-risk/anemia/transfusion-dependent MDS, transfusion independence/burden was the top endpoint family at 9 of 11 trials (81.8%).
| Disease subtype | Trials | Most frequent endpoint |
|---|---|---|
| AML / MDS-AML overlap | 33 / 55 | Safety: 29 / 33 · 87.9% |
| Higher-risk / excess-blast MDS | 16 / 55 | Safety: 16 / 16 · 100.0% |
| Lower-risk / anemia / transfusion-dependent MDS | 11 / 55 | Transfusion endpoints: 9 / 11 · 81.8% |
| MDS/MPN or CMML overlap | 10 / 55 | Safety: 9 / 10 · 90.0% |
| Mutation/biology-defined MDS | 6 / 55 | Safety: 6 / 6 · 100.0% |
The MDS trial landscape is strongly shaped by AML-adjacent biology and progression risk. Lower-risk MDS is the main exception: its endpoint architecture is much more transfusion- and anemia-benefit oriented.
Small molecules appeared in 40 of 55 trials (72.7%). Peptide/protein/enzyme interventions appeared in 11 trials (20.0%), monoclonal antibodies in 4 trials (7.3%), cell therapy in 3 trials (5.5%), other antibodies in 2 trials (3.6%), and ADC or oligonucleotide in 1 trial each (1.8%). Among small molecule trials, safety appeared in 36 of 40 (90.0%); among peptide/protein/enzyme trials, transfusion independence/burden appeared in 9 of 11 (81.8%).
Small molecules remain the backbone of European MDS development and therefore define the broad endpoint baseline. Peptide/protein/enzyme programs are more visibly tied to anemia and transfusion-benefit endpoints.
The dataset includes 36 trials first authorized in CTIS during 2024, 16 during 2025, and 3 during 2026. Across all 55 trials, the median interval from initial CTIS submission to first CTIS authorization was 45 days, with an interquartile range of 28 to 96 days.
For EU submission planning, MDS trial endpoint packages should be CTIS-ready with explicit safety, response, survival, AML-progression, and transfusion definitions before initial submission, because these domains recur across most authorized programs.
MDS means myelodysplastic syndrome. AML means acute myeloid leukemia. OS means overall survival. EFS means event-free survival. MRD means measurable or minimal residual disease. PRO means patient-reported outcome. GvHD means graft-versus-host disease. NRM means non-relapse mortality. CTIS means Clinical Trials Information System, the EU clinical trial submission and authorization platform.