The number and breadth of therapeutic trials with development efforts focused on the limited population of individuals with CF ineligible for, or intolerant of or non-responsive to, CFTR modulators is extensive and successful completion of multiple clinical development programs will depend on
Increasing the number of participants willing and able to participate in therapeutic trials through community engagement, education, and equitable methodology and infrastructure for communication of trial opportunities, Increased prioritization of therapies as they enter and progress through the therapeutic pipeline with global alignment across CF clinical trial networks, balancing the communities needs with the need to support the interests of multiple engaged sponsors pursuing therapeutic indications in CF, and Innovative trial designs that streamline clinical development programs including maximizing the use of external control and natural history data.
Efforts to expand therapeutic development to individuals residing in low- and middle- income countries (LMICs), many of whom are disproportionately affected by lack of access or eligibility for CFTR modulators due to a higher prevalence of non-F508del mutations, is critically contingent on strategies and advocacy to ensure equitable access to therapies that achieve regulatory approval. Investment in strategies to ensure comparable diagnosis, standards of care and outcomes in these countries will be essential to facilitate expansion of clinical trial development efforts to the global community. Development of new therapies to benefit those without modulators will likely require continued contributions from those on modulators, such as to help establish early phase safety of new therapies, despite new challenges gauging interest in trial participation and assessing clinical efficacy signals in a population benefitting from highly effective modulators. Advancement of alternative clinical outcomes to establish the clinical efficacy of a new therapeutic agent will be needed particularly when including the population of those with CF on highly effective CFTR modulators with more mild and stable pulmonary disease. Successful clinical development of new symptomatic therapies may be enabled through supporting proposed indications and trials which combine populations from multiple diseases that share key features with those of the CF population. There remains an important need for investigator-initiated studies to address research questions that will not be investigated by industry-sponsored trials. The complexity of evaluating research questions that align with the priorities of the CF community amidst a dynamic and incompletely characterized population with changing disease manifestations in response to highly effective CFTR modulators highlights the need for increased global partnership.
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