Across 239 CTIS-authorized European respiratory Phase II and Phase III trials, safety and tolerability were the most common endpoint family, appearing in 150/239 trials (62.8%). Patient-reported outcomes, symptoms, and quality-of-life measures followed in 131/239 trials (54.8%), while biomarker or diagnostic endpoints appeared in 107/239 trials (44.8%). Endpoint selection was strongly disease-shaped: FVC dominated pulmonary fibrosis/ILD, exacerbations dominated asthma and COPD, and RECIST/RANO response plus survival dominated lung cancer.
At trial level, safety/tolerability appeared in 150/239 trials (62.8%), patient-reported outcomes (PROs), symptoms, or quality of life (QoL) in 131/239 (54.8%), and biomarkers/diagnostics in 107/239 (44.8%). A trial could count once per endpoint family if that endpoint appeared in any primary, secondary, or exploratory role.
Respiratory Phase II/III endpoint design is not defined by one pulmonary physiology measure. Safety, PRO/QoL, biomarkers, survival, and clinical worsening appear more often than FEV1 or FVC because the CTIS respiratory cohort spans airway disease, fibrotic lung disease, lung cancer, infection, neonatal/critical care, and pulmonary vascular disease.
Among 230 trials with primary endpoint entries, safety/tolerability led with 51/230 trials (22.2%), followed by survival/mortality in 33/230 (14.3%), PROs/QoL in 29/230 (12.6%), and FVC/ppFVC in 25/230 (10.9%). Among 210 trials with secondary endpoint entries, PROs/QoL appeared in 119/210 (56.7%), safety in 114/210 (54.3%), and biomarkers/diagnostics in 99/210 (47.1%). Exploratory endpoints were present in 8/239 trials (3.3%).
Primary endpoints reflect disease-specific regulatory logic: safety for early or high-risk studies, FVC for fibrotic lung disease, exacerbations for obstructive airway disease, and response/survival for lung cancer. Secondary endpoints are broader and repeatedly add patient experience, safety, biomarker, and clinical-worsening dimensions.
In Phase II trials (n=120), safety/tolerability appeared in 86/120 trials (71.7%), PROs/QoL in 62/120 (51.7%), biomarkers in 57/120 (47.5%), and PK/dose exposure in 41/120 (34.2%). In Phase III trials (n=119), PROs/QoL led with 69/119 trials (58.0%), followed by safety in 64/119 (53.8%), biomarkers and clinical worsening in 50/119 each (42.0%), and survival/mortality in 43/119 (36.1%).
The Phase II respiratory portfolio remains more dose- and safety-discovery oriented, with PK/dose exposure twice as common as in Phase III. Phase III trials more often add clinical-worsening, hospitalization, and patient-experience endpoints, consistent with confirmatory outcome packages.
The largest disease groups were lung cancer (38/239, 15.9%), respiratory infection (32/239, 13.4%), pulmonary fibrosis/ILD (29/239, 12.1%), asthma (26/239, 10.9%), and COPD/emphysema (25/239, 10.5%). In disease groups with at least 8 trials, the dominant endpoint families were sharply different: tumour response and survival in lung cancer, FVC in pulmonary fibrosis/ILD, infection/safety endpoints in respiratory infections, exacerbations and FEV1 in asthma/COPD, and 6MWD/PVR/functional class in pulmonary hypertension.
The broad respiratory label hides distinct development logics. Fibrosis studies are physiology-led, asthma and COPD are exacerbation and symptom-led, pulmonary hypertension is functional/hemodynamic-led, and lung cancer is oncology-led despite being captured inside the respiratory CTIS cohort.
Among disease groups with at least 8 trials, the most frequent primary endpoint family was FVC/ppFVC in pulmonary fibrosis/ILD (19/29, 65.5%), PRO/QoL in upper-airway allergy/CRS (7/8, 87.5%), 6MWD/PVR/functional class in pulmonary hypertension (6/11, 54.5%), safety in cystic fibrosis (6/10, 60.0%), tumour response in lung cancer (16/38, 42.1%), exacerbations in COPD/emphysema (10/25, 40.0%), and exacerbations in asthma (8/26, 30.8%).
Primary endpoint selection is highly anchored where disease conventions are mature: FVC for fibrosis, 6MWD/PVR/functional class for pulmonary hypertension, RECIST/RANO response for lung cancer, and exacerbation outcomes for COPD and asthma. Safety becomes a primary anchor mainly where the studied population or modality is higher risk.
Five modality groups had at least 20 trials: small molecules (99/239, 41.4%), small molecule plus monoclonal antibody combinations (31/239, 13.0%), monoclonal antibodies (29/239, 12.1%), protein/peptide therapies (21/239, 8.8%), and mixed combinations (20/239, 8.4%). Small molecule trials most often used safety (63/99, 63.6%) and PRO/QoL endpoints (58/99, 58.6%); monoclonal antibody trials most often used PRO/QoL endpoints (20/29, 69.0%) and had immunogenicity/ADA-nAb endpoints in 9/29 trials (31.0%).
The modality signal is partly confounded by disease mix, but still operationally useful: small molecules and combinations carry broad safety packages, mAbs add immunogenicity and biomarker layers, and oncology-style small molecule plus mAb combinations concentrate response and survival endpoints.
Across all 239 respiratory Phase II/III trials, the median time from initial CTIS submission to first CTIS authorization was 104 days. Phase II trials had a median of 106 days, and Phase III trials had a median of 102 days. By CTIS authorization year, the median was 82 days for 2024-authorized trials, 112 days for 2025-authorized trials, and 114 days for 2026-authorized trials.
The CTIS timing pattern suggests that endpoint complexity is not the only operational variable: both Phase II and Phase III respiratory submissions had similar authorization medians, while the authorization-year cohorts shifted upward after 2024. This is useful context for planning EU respiratory submissions under CTIS.
Endpoint families were counted at trial level. A trial could contribute to multiple endpoint families if different endpoint measures appeared in its primary, secondary, or exploratory endpoint text.