Expanding the indication of CFTR modulator combinations for people with cystic fibrosis with non-F508del variants
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CFTR modulators are small molecules that bind to defective CFTR proteins in people with cystic fibrosis, partly restoring chloride transport, and were discovered thanks to high-throughput screening.1 Treatment with the single CFTR modulator ivacaftor induces substantial improvement in chloride transport and clinical status in people with cystic fibrosis with gating variants. Restoring chloride transport to 40–50% of normal CFTR function, the threshold that is widely understood to be associated with clinical benefits in carriers of a least one F508del (also known as Phe508del) variant, requires a combination of CFTR modulators with different mechanisms of action.1 Elexacaftor–tezacaftor–ivacaftor (ETI) has become the current standard of care for the approximately 82% of the global cystic fibrosis population with at least one F508del variant.2 The remaining 18% are currently not eligible for ETI in most countries.
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