Across 57 European CTIS phase-specific multiple sclerosis trial records authorized from 2024 to 2026, endpoint measurement is broad but not evenly weighted. Safety/tolerability appears in 45/57 records (78.9%), MRI lesion activity in 39/57 (68.4%), and confirmed disability, Expanded Disability Status Scale (EDSS), or functional progression in 38/57 (66.7%). Primary endpoints are more efficacy-led, with MRI lesion activity leading at 16/57 records (28.1%), while secondary endpoints carry most safety, biomarker, pharmacokinetic, patient-reported, and functional burden.
Safety/tolerability is the most frequent endpoint family, appearing in 45/57 records (78.9%). The two leading efficacy families are MRI lesion activity in 39/57 records (68.4%) and confirmed disability, EDSS, or functional progression in 38/57 records (66.7%).
The endpoint backbone is still built around conventional MS efficacy signals: inflammatory lesion activity, confirmed disability/function, and relapse. However, the most universal measurement layer is safety, which appears in nearly four out of five records.
Primary endpoints concentrate on efficacy: MRI lesion activity appears as a primary family in 16/57 records (28.1%), relapse/annualized relapse rate (ARR) in 14/57 (24.6%), and disability/EDSS/function in 12/57 (21.1%). Secondary endpoints are much broader, led by safety in 41/57 records (71.9%), MRI lesion activity in 36/57 (63.2%), and disability/EDSS/function in 35/57 (61.4%).
| Endpoint family | Primary | Secondary | Exploratory |
|---|---|---|---|
| Safety / tolerability | 12 /57 | 41 /57 | 1 /57 |
| MRI lesion activity | 16 /57 | 36 /57 | 0 /57 |
| Confirmed disability / EDSS / function | 12 /57 | 35 /57 | 0 /57 |
| PRO / cognition / symptoms | 4 /57 | 34 /57 | 0 /57 |
| Biomarkers / immune profiling | 1 /57 | 26 /57 | 1 /57 |
| Relapse / ARR | 14 /57 | 22 /57 | 0 /57 |
| PK / exposure | 4 /57 | 22 /57 | 0 /57 |
| Brain volume / atrophy | 8 /57 | 17 /57 | 0 /57 |
| Immunogenicity / ADA | 0 /57 | 13 /57 | 0 /57 |
| NEDA / composite disease activity | 3 /57 | 7 /57 | 0 /57 |
| Health economics / resource use | 0 /57 | 4 /57 | 0 /57 |
MS trials rarely label endpoints as exploratory: 5 exploratory endpoint entries appear across 1/57 records (1.8%). Most operational and mechanistic measurement depth is therefore placed in the secondary endpoint tier rather than the exploratory tier.
The cohort contains 24 Phase II records (42.1%) and 33 Phase III records (57.9%). Phase II records emphasize safety (18/24; 75.0%), disability/function and PRO/cognition/symptom endpoints (16/24 each; 66.7%), while Phase III records show stronger relapse use (21/33; 63.6%) alongside safety (27/33; 81.8%) and MRI lesion activity (25/33; 75.8%).
| Endpoint family | Phase II | Phase III |
|---|---|---|
| Safety / tolerability | 18 /24 (75.0%) | 27 /33 (81.8%) |
| MRI lesion activity | 14 /24 (58.3%) | 25 /33 (75.8%) |
| Confirmed disability / EDSS / function | 16 /24 (66.7%) | 22 /33 (66.7%) |
| PRO / cognition / symptoms | 16 /24 (66.7%) | 19 /33 (57.6%) |
| Biomarkers / immune profiling | 12 /24 (50.0%) | 15 /33 (45.5%) |
| Relapse / ARR | 6 /24 (25.0%) | 21 /33 (63.6%) |
| PK / exposure | 8 /24 (33.3%) | 16 /33 (48.5%) |
| Brain volume / atrophy | 7 /24 (29.2%) | 14 /33 (42.4%) |
| Immunogenicity / ADA | 5 /24 (20.8%) | 8 /33 (24.2%) |
| NEDA / composite disease activity | 3 /24 (12.5%) | 7 /33 (21.2%) |
The main phase signal is relapse: it appears in 21/33 Phase III records (63.6%) versus 6/24 Phase II records (25.0%). Phase II is more exploratory in measurement mix, with PRO/cognition/symptom endpoints matching disability/function at 16/24 records (66.7%).
Relapsing/RRMS-spectrum records are the largest subtype group, appearing in 28/57 records (49.1%), followed by progressive/PPMS-SPMS-spectrum records in 19/57 (33.3%) and broad unspecified MS records in 14/57 (24.6%). Relapsing records emphasize safety, MRI lesions, and relapse; progressive records concentrate more heavily on disability/function and brain volume/atrophy.
Progressive MS records show the clearest disability-centered design: 18/19 records (94.7%) contain disability, EDSS, or functional progression endpoints. Relapsing-spectrum records retain the classic inflammatory disease-control stack: safety in 24/28 (85.7%), MRI lesions in 21/28 (75.0%), and relapse/ARR in 18/28 (64.3%).
Small molecules appear in 39/57 records (68.4%) and monoclonal antibodies in 30/57 records (52.6%), making them the most comparable modality groups. Safety is especially frequent in monoclonal antibody records (28/30; 93.3%), while small-molecule records spread more evenly across safety (28/39; 71.8%), MRI lesions (27/39; 69.2%), and disability/function (27/39; 69.2%).
Monoclonal antibody records have a heavier safety and PK/immune-monitoring footprint: safety appears in 28/30 records (93.3%), PK/exposure in 17/30 (56.7%), and biomarkers/immune profiling in 17/30 (56.7%). Cell therapy records are fewer but show a concentrated multidomain profile, with safety and disability/function present in 5/5 records (100.0%).
The dataset also shows where endpoint burden sits and how quickly CTIS-submitted MS records moved from initial EU submission to first authorization. Across 573 extracted endpoint entries, 494 are secondary (86.2%), 74 are primary (12.9%), and 5 are exploratory/other (0.9%).
Endpoint complexity sits mainly outside the primary endpoint: secondary endpoints account for 494/573 extracted entries (86.2%). For EU/CTIS planning, Phase III records moved faster by median submission-to-authorization interval than Phase II records: 52.0 days versus 102.5 days.
ARR means annualized relapse rate. EDSS means Expanded Disability Status Scale. CDP/CDW refer to confirmed disability progression or worsening. MRI lesion activity includes gadolinium-enhancing T1 lesions, new or enlarging T2 lesions, FLAIR activity, and related radiological disease-activity endpoints. PRO includes patient-reported outcomes, quality of life, symptom scales, fatigue, pain, spasticity, and cognitive measures such as Symbol Digit Modalities Test (SDMT).
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