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 language | English (US) |
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Pages (from-to) | 932-944 |
Number of pages | 13 |
Journal | The Lancet Respiratory Medicine |
Volume | 11 |
Issue number | 10 |
DOIs | |
State | Published - 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