Across 463 unique EU CTIS neurology Phase II & III trials authorized in 2024–2026, safety/tolerability was the most frequent endpoint family, appearing in 300 trials (64.8%). Biomarker or target-engagement endpoints appeared in 231 trials (49.9%), clinical function or disability scales in 227 (49.0%), and quality-of-life or patient-reported outcomes in 225 (48.6%). Phase II trials leaned more heavily toward safety, biomarkers, imaging, and pharmacokinetics, while Phase III trials shifted toward functional, event-based, symptom, and quality-of-life endpoints.
Safety/tolerability endpoints appeared in 300 of 463 trials (64.8%), making them the most common endpoint family across all endpoint roles. Biomarkers or target engagement followed in 231 trials (49.9%), clinical function/disability in 227 (49.0%), and quality-of-life or patient-reported outcomes in 225 (48.6%).
European neurology endpoint strategy is not led by a single disease-specific measure. EU CTIS submissions most often combine regulatory safety capture with biological proof-of-mechanism, functional outcomes, and patient-reported impact.
Primary endpoints were most often safety/tolerability endpoints, present in 137 of 463 trials (29.6%). Secondary endpoints were broader: quality-of-life or patient-reported outcomes appeared in 215 trials (46.4%), clinical function/disability in 208 (44.9%), safety in 205 (44.3%), and biomarkers in 204 (44.1%). Exploratory or other endpoint fields were uncommon, appearing in 9 trials (1.9%).
| Endpoint role | Most frequent families | Trials |
|---|---|---|
| Primary | Safety / tolerability | 137/463 · 29.6% |
| Disease activity / relapse / events | 96/463 · 20.7% | |
| Clinical function / disability | 84/463 · 18.1% | |
| Secondary | Quality of life / PROs | 215/463 · 46.4% |
| Clinical function / disability | 208/463 · 44.9% | |
| Safety / tolerability | 205/463 · 44.3% | |
| Exploratory / other | Biomarkers and safety were tied | 5/9 · 55.6% |
The EU submission pattern is primary-endpoint discipline plus secondary-endpoint breadth. Primary endpoints concentrate on safety, events, function and imaging, while secondary endpoints absorb QoL, function, biomarkers, cognition, PK and symptom burden.
Multiple sclerosis was the largest defined disease group with 56 trials (12.1%), followed by Alzheimer’s/dementia with 49 (10.6%), stroke/cerebrovascular disease with 47 (10.2%), and neuromuscular/neuropathy disorders with 40 (8.6%). Disease-specific endpoint signatures were clear: multiple sclerosis centered on MRI lesion burden, Alzheimer’s/dementia on cognition, stroke on functional status, migraine on pain/symptom intensity, and myasthenia gravis on functional disability scales.
| Disease group | Trials | Dominant endpoint family | Share |
|---|---|---|---|
| Multiple sclerosis | 56 | Imaging / MRI lesion burden | 45/56 · 80.4% |
| Alzheimer’s / dementia | 49 | Cognition / neuropsychology | 29/49 · 59.2% |
| Stroke / cerebrovascular | 47 | Clinical function / disability | 32/47 · 68.1% |
| Neuromuscular / neuropathy | 40 | Safety / tolerability | 34/40 · 85.0% |
| Movement disorders | 33 | Safety / tolerability | 20/33 · 60.6% |
| Migraine / headache | 25 | Pain / symptom intensity | 21/25 · 84.0% |
| Neuro-oncology / CNS tumors | 23 | Disease activity / response | 15/23 · 65.2% |
| ALS / motor neuron disease | 22 | Safety and biomarkers tied | 17/22 · 77.3% |
| Myasthenia gravis | 21 | Clinical function / disability | 20/21 · 95.2% |
| Epilepsy / seizure disorders | 21 | Disease activity / seizure events | 16/21 · 76.2% |
Disease biology drives endpoint selection more strongly than therapeutic area alone. A CTIS neurology submission in multiple sclerosis is likely to require MRI lesion endpoints, while myasthenia gravis and stroke submissions are more anchored in functional disability scales.
Within the 56 multiple sclerosis trials, relapsing forms accounted for 27 trials (48.2%), progressive forms for 15 (26.8%), and unspecified multiple sclerosis for 14 (25.0%). MRI or imaging endpoints appeared in 45 of 56 multiple sclerosis trials (80.4%), and were primary endpoints in 21 of 56 trials (37.5%).
Multiple sclerosis is the clearest sub-disease example because it has enough trial volume and a consistent endpoint backbone. Imaging is the dominant EU neurology MS endpoint layer, especially MRI lesion burden and disease-activity measures such as relapse or NEDA-style composites.
The Phase II and Phase III CTIS phase views each contained 247 trial records. Phase II was more biomarker- and mechanism-heavy: safety appeared in 179/247 Phase II records (72.5%), biomarkers in 159 (64.4%), imaging in 91 (36.8%), and pharmacokinetics in 74 (30.0%). Phase III placed more weight on patient-relevant clinical endpoints: clinical function appeared in 131/247 records (53.0%), quality of life in 130 (52.6%), and disease activity or event endpoints in 115 (46.6%).
| Endpoint family | Phase II | Phase III |
|---|---|---|
| Safety / tolerability | 179/247 · 72.5% | 144/247 · 58.3% |
| Biomarkers / target engagement | 159/247 · 64.4% | 93/247 · 37.7% |
| Clinical function / disability | 111/247 · 44.9% | 131/247 · 53.0% |
| Quality of life / PROs | 113/247 · 45.7% | 130/247 · 52.6% |
| Disease activity / events | 76/247 · 30.8% | 115/247 · 46.6% |
| Pharmacokinetics / exposure | 74/247 · 30.0% | 47/247 · 19.0% |
The Phase II endpoint profile is still heavily translational, while Phase III increasingly reflects regulatory confirmation: functional status, disease events, symptoms and quality of life become more prominent than pure PK or target-engagement measures.
Small molecules were the largest modality group, appearing in 276 of 463 trials (59.6%). Antibody, oligonucleotide and gene-therapy trials showed a stronger safety/biomarker burden: safety appeared in 79/94 monoclonal antibody trials (84.0%), 19/23 oligonucleotide trials (82.6%), and 18/20 gene therapy trials (90.0%).
| Modality | Trials | Endpoint signature |
|---|---|---|
| Small molecule | 276 | Safety 179/276 (64.9%); QoL/PRO 159/276 (57.6%) |
| Monoclonal antibody | 94 | Safety 79/94 (84.0%); biomarkers 66/94 (70.2%) |
| Peptide/protein/enzyme | 69 | Safety 46/69 (66.7%); biomarkers 43/69 (62.3%) |
| Oligonucleotide | 23 | Safety 19/23 (82.6%); biomarkers 18/23 (78.3%) |
| Gene therapy | 20 | Safety 18/20 (90.0%); biomarkers 15/20 (75.0%) |
Advanced and biologic modalities create heavier CTIS endpoint packages. Antibodies, oligonucleotides and gene therapies show higher use of safety, biomarker and PK-style endpoints than small molecules, reflecting immunogenicity, exposure, target-engagement and long-term risk questions.
Pediatric trials accounted for 114 of 463 trials (24.6%). Orphan-drug trials accounted for 90 (19.4%). Orphan-drug trials showed particularly high endpoint density around safety, function, biomarkers and quality of life: safety appeared in 73/90 orphan trials (81.1%), function in 56 (62.2%), biomarkers in 55 (61.1%), and QoL/PROs in 54 (60.0%).
For rare and pediatric neurology trials, EU submission strategy needs more than a single efficacy endpoint. Safety, function, biomarkers and QoL commonly travel together, especially where disease rarity or vulnerable populations increase evidentiary uncertainty.
The dataset supports a current EU submission-timing view. Of the 463 unique CTIS neurology trials, 246 were first authorized in 2024, 151 in 2025, and 66 in 2026. Across all authorization years, safety remained the top endpoint family: 161/246 trials in 2024 (65.4%), 94/151 in 2025 (62.3%), and 45/66 in 2026 (68.2%). Median time from initial CTIS submission to first authorization was 98 days.
| Year | Trials | Top endpoint families |
|---|---|---|
| 2024 | 246 | Safety 161/246 (65.4%); QoL/PROs 129/246 (52.4%); biomarkers 128/246 (52.0%) |
| 2025 | 151 | Safety 94/151 (62.3%); biomarkers 74/151 (49.0%); function 69/151 (45.7%) |
| 2026 | 66 | Safety 45/66 (68.2%); function 34/66 (51.5%); QoL/PROs 30/66 (45.5%) |
Recent EU neurology submissions show stable reliance on safety endpoints, with biomarkers and functional endpoints consistently among the strongest supporting measures. For CTIS planning, the endpoint package should be built as a multi-domain dossier rather than as a single-outcome protocol story.
Endpoint families were grouped at trial level: a trial counted once per family if at least one primary, secondary, or exploratory endpoint matched that family.