Differential access to CFTR modulators leads to divergent patient populations
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CFTR modulators associated with substantial clinical benefit reset the baseline condition of patients with CF
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New clinical trial paradigms are needed to test new treatments in this context
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In general, only trials with short placebo periods will be acceptable
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Efficacy extrapolation from cellular models will be necessary for rare CFTR mutations
Abstract
CFTR modulators associated with substantial clinical benefit are expected to rapidly improve the baseline condition of people with cystic fibrosis (PWCF) as well as decrease the rate of lung function decline, the occurrence of pulmonary exacerbations and likely even other disease complications. These changes in clinical status of PWCF introduced by clinically effective modulator therapy will have major repercussions on modalities of future CF drug development.
As part of its ‘Strategic Plan to speed up Access to new Drugs’, the European Cystic Fibrosis Society (ECFS) convened a meeting in Brussels on November 27th 2019 with relevant stakeholders (CF researchers and clinicians, patient organization and pharmaceutical company representatives, regulators, health technology assessors; see Acknowledgments for list of attendees) to discuss the future of clinical trials in cystic fibrosis (CF) in the context of HEMT entering the clinical arena. The following is the conclusion of the presentations and discussions. It is hoped that these concepts will be considered in future regulatory guidelines and may provide rationale and support for alternative trial designs.
