PRenatal mOdulator treatment to PrEvent CF complicaTions (PROTECT) workshop report

Area of Science:

• Medical Research
• Pharmacology
• Genetics

Background:

• Emerging data from animal models and case studies suggest in utero administration of CFTR modulators (variant specific therapies, VST) may mitigate CF pathophysiology in the fetus.
• The use of VST during pregnancy to prevent infant CF has not been systematically evaluated.

Purpose of the Study:

• To assess stakeholder awareness and gather expert opinion on the potential for in utero VST therapy for fetal CF.
• To determine if formal research evaluation of in utero VST is warranted.

Main Methods:

• Survey of CF care center directors regarding awareness of off-label VST use for fetal CF treatment.
• International multidisciplinary workshop to review pre-clinical/clinical data, embryology, and regulatory considerations.

Main Results:

• High awareness (92%) among surveyed directors regarding VST use for fetal CF prevention.
• Expert consensus suggests VST is relatively safe and effective in animal models and case series for mitigating fetal CF complications.
• Identified knowledge gaps include optimal timing, pharmacokinetics, dosing during pregnancy/lactation, and long-term infant safety.

Conclusions:

• Stakeholders concluded that formal evaluation of in utero and early life VST therapy in a prospective trial is warranted based on current data and identified gaps.