PULMONARY FIBROSIS · White paper
Pulmonary Fibrosis (IPF) Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About pulmonary fibrosis (ipf) — and why its trials are hard
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease marked by scarring of lung parenchyma, a usual interstitial pneumonia (UIP) pattern on high-resolution CT, and a poor prognosis with median survival of roughly 3-5 years after diagnosis. Understanding has shifted from viewing IPF as a variant of interstitial pneumonia toward a distinct entity driven by epithelial injury, aberrant wound healing, and fibroblast activation, with genetic contributors such as TERT/TERC telomere-related mutations. The defining trial endpoint is the rate of decline in forced vital capacity (FVC), supported by DLCO, HRCT extent of fibrosis, and the six-minute walk test. Two oral antifibrotics anchor therapy: pirfenidone (ASCEND) and nintedanib (INPULSIS), both approved in 2014 and both shown to slow FVC decline rather than reverse disease. The field is notable for repeated late-stage failures - including ambrisentan (harmful in IPF), pamrevlumab, ziritaxestat, and simtuzumab - underscoring disease heterogeneity, weak preclinical models, and a shortage of validated early biomarkers.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Pirfenidone (Esbriet) | 2014 | Idiopathic pulmonary fibrosis (antifibrotic; inhibits TGF-beta and PDGF) | ASCEND (NCT01366209) | Change in % predicted FVC / FVC decline over 52 weeks | Reduced FVC decline by ~47.9% vs placebo; fewer patients with >=10% FVC decline (17% vs 32%) |
| Nintedanib (Ofev) | 2014 | Idiopathic pulmonary fibrosis (tyrosine kinase inhibitor; VEGFR/FGFR/PDGFR) | INPULSIS-1 & INPULSIS-2 (NCT01335464) | Annual rate of FVC decline (mL/year); time to first exacerbation | Annual FVC decline reduced ~50% (e.g., -114.7 vs -239.9 mL/yr); exacerbation HR 0.38 (pooled) |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in pulmonary fibrosis (ipf) development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Ambrisentan — ARTEMIS-IPF | Terminated early; harmful - higher rates of death, respiratory hospitalization, and FVC/DLCO decline (8% vs 4% death) | Endothelin antagonism worsened outcomes in IPF (WHO Group 3), showing pulmonary vasodilator harm in fibrosis |
| Pamrevlumab — NCT03955146 (ZEPHYRUS) | Failed to meet the Phase 3 primary endpoint | Persistent difficulty demonstrating antifibrotic efficacy despite promising anti-CTGF mechanism |
| Ziritaxestat — NCT03711162 / NCT03733444 (ISABELA) | Lack of efficacy; trials stopped early | Autotaxin inhibition did not translate from preclinical models to clinical FVC benefit |
Choosing the right endpoint
Primary endpoints that matter in pulmonary fibrosis (ipf) trials
- Forced Vital Capacity (FVC) — Primary endpoint (absolute or % predicted decline); lower FVC signals worse prognosis, but measurement varies with technique and patient effort
- DLCO — Diffusing capacity for carbon monoxide; reflects gas-exchange efficiency but is confounded by conditions such as anemia
- HRCT extent of fibrosis — High-resolution CT quantifies fibrosis and UIP pattern; interpretation varies among radiologists, requiring standardized protocols
- Six-Minute Walk Test (6MWT) — Functional exercise-capacity measure; sensitive to motivation and external conditions, so requires standardized administration
- Time to acute exacerbation / all-cause mortality — Clinically meaningful event endpoints; mortality trials showed non-significant trends for both antifibrotics, highlighting the need for long follow-up
How iNGENū runs pulmonary fibrosis (ipf) trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
The full white paper: approved-product analyses, pivotal endpoints and trial-design strategy. Open-access · no sign-in.
Frequently asked questions
Pulmonary Fibrosis (IPF) clinical trials — FAQs
What is the key efficacy endpoint in IPF trials?
Which drugs are approved for IPF and what do they do?
Why have so many IPF drug candidates failed?
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