"Regression to the truth": lessons learned from negative IPF trials.
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with limited treatment options. Despite the approval of pirfenidone and nintedanib that slow disease progression, IPF remains a disease with poor survival. Promising therapeutic candidates were tested as potential treatments for IPF and w...
| Publicado en: | Breathe Vol. 21; no. 2; pp. 1 - 8 |
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| Autores principales: | , , , |
| Formato: | questions and answers tables/charts Journal Article |
| Publicado: |
European Respiratory Society
Apr2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=185791030&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 185791030 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 18106838 85SQ jtl: Breathe issn: 18106838 maglogo: N pubinfo: dt: Apr2025 vid: 21 iid: 2 pid: 76609 pub: European Respiratory Society artinfo: ui: 185791030 185791030 185791030 10.1183/20734735.0260-2024 185791030 ppf: 1 ppct: 7 formats: fmt: @attributes: type: P tig: atl: "Regression to the truth": lessons learned from negative IPF trials. aug: au: Trachalaki, Athina Lindahl, Anna L. Petrarulo, Simone Margaritopoulos, George A. affil: Margaret Turner Warwick Centre for Fibrosing Lung Disease, National Heart and Lung Institute, Imperial College London, London, UK sug: subj: Idiopathic Pulmonary Fibrosis Drug Therapy Drugs, Investigational Therapeutic Use Antibodies, Monoclonal Therapeutic Use Drug Efficacy Drug Development Small Molecules Sample Size Study Design ab: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with limited treatment options. Despite the approval of pirfenidone and nintedanib that slow disease progression, IPF remains a disease with poor survival. Promising therapeutic candidates were tested as potential treatments for IPF and while some drugs were successful in phase II clinical trials, their successful transition to positive phase III was unfortunately disappointing. This highlights the "regression to the truth" concept in drug development, whereby positive phase II trial results may simply be a statistical anomaly rather than the result of true efficacy. We examine three pivotal trials of novel IPF therapies, zinpentraxin alfa, ziritaxestat and pamrevlumab, that failed in late-stage clinical development. These failures underscore common pitfalls in IPF drug development, including inadequate phase II sample sizes, reliance on surrogate endpoints like forced vital capacity, and challenges integrating background antifibrotic therapies. Moving forward, innovative approaches like adaptive trial designs, Bayesian statistics and composite endpoints could improve trial robustness. Moreover, platform trials may accelerate drug development by testing multiple therapies simultaneously. Negative trials are not failures but opportunities for learning. By recognising and addressing these challenges, while also embracing novel trial methodologies, we can enhance drug development and improve IPF outcomes. pubtype: Academic Journal doctype: questions and answers tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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