Non-eligibility for highly effective modulator therapy with elexacaftor/tezacaftor/ivacaftor in cystic fibrosis: What about Portugal?

BACKGROUND

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR modulators are drugs developed to target the defective protein. All over the world, there are patients considered non-eligible for this therapy according to local regulatory policies.

METHODS

To characterise the Portuguese CF patients defined as non-eligible according to genotype for highly effective modulator therapy (HEMT) with elexacaftor/tezacaftor/ivacaftor (ETI), the authors conducted a multicentre observational study based on a retrospective analysis of the Portuguese CF population.

RESULTS

Based on the current prescribing policy in Portugal, the prevalence of non-eligible patients in Portugal in 2023 was 18.7%, similar to that reported in Europe. However, the regulatory acceleration in the CFTR modulator landscape in 2025 will most likely decrease the expected prevalence to 1.2% under national regulatory adoption of EMA criteria. R334W, G85E, N1303K, G542X, A561E, R1066C and P205S are the most prevalent variants. Most patients are young adults with established pulmonary disease. CF therapies impose a considerable burden on this population.

CONCLUSION

This study provides a deeper understanding of the Portuguese CF population currently ineligible for ETI and enables the projection of the potential impact that forthcoming changes in HEMT eligibility criteria may have across Portugal. With the anticipated expansion of these criteria, the number of patients remaining ineligible for HEMT is expected to become residual. Furthermore, the present work offers a characterisation of patients likely to remain ineligible for HEMT in the future, who could be suitable candidates for clinical trials exploring alternative therapeutic approaches.