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.
We continuously analyze new and updated clinical trial data and publish practical, evidence-led reports for clinical leaders.
