Advancing the pipeline of cystic fibrosis clinical trials: a new roadmap with a global trial network perspective

Nicole Mayer-Hamblett*, John Paul Clancy, Raksha Jain, Scott H. Donaldson, Isabelle Fajac, Christopher H. Goss, Deepika Polineni, Felix Ratjen, Bradley S. Quon, Edith T. Zemanick, Scott C. Bell, Jane C. Davies, Manu Jain, Michael W. Konstan, Natanya R. Kerper, Tré LaRosa, Marcus A. Mall, Edward McKone, Kelsie Pearson, Joseph M. PilewskiLynne Quittell, Jonathan H. Rayment, Steven M. Rowe, Jennifer L. Taylor-Cousar, George Retsch-Bogart, Damian G. Downey

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations

Abstract

The growing use of modulator therapies aimed at restoring cystic fibrosis transmembrane conductance regulator (CFTR) protein function in people with cystic fibrosis has fundamentally altered clinical trial strategies needed to advance new therapeutics across an orphan disease population that is now divided by CFTR modulator eligibility. The development of a robust pipeline of nucleic acid-based therapies (NABTs)—initially directed towards the estimated 10% of the cystic fibrosis population who are genetically ineligible for, or intolerant of, CFTR modulators—is dependent on the optimisation of restricted trial participant resources across multiple development programmes, a challenge that will preclude the use of gold standard placebo-controlled trials. Advancement of a full pipeline of symptomatic therapies across the entire cystic fibrosis population will be challenged by smaller effect sizes and uncertainty regarding their clinical importance in a growing modulator-treated population with more mild and stable pulmonary disease. In this Series paper, we aim to lay the foundation for clinical trial strategy and community partnership that must deviate from established and familiar precedent to advance the future pipeline of cystic fibrosis therapeutics.

Original languageEnglish (US)
Pages (from-to)932-944
Number of pages13
JournalThe Lancet Respiratory Medicine
Volume11
Issue number10
DOIs
StatePublished - Oct 2023

Funding

We thank the Cystic Fibrosis Foundation for funding the Cystic Fibrosis Therapeutic Development Research Workshop. No funding was received for the writing of this Series paper, the content of which is the responsibility of the authors alone and does not necessarily reflect the views or policies of the workshop sponsor. We thank the people with cystic fibrosis who participate in and contribute to clinical research efforts across the world. It is their dedication and engagement that will be crucial to drive the future of cystic fibrosis clinical trials.

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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