Jennifer Taylor-Cousar, MD, MSCS, on early signs of gene therapy efficacy in cystic fibrosis

“All 3 doses showed good expression in the airways. In the cohorts dosed with the lower doses, we also showed that people tolerated the drug and that at least in the 1×10¹⁵ At least one person with a vector genome dose had a clinically meaningful improvement in percent predicted lung function. Therefore, we think it would be very promising to test this or lower doses in additional participants.”

4D Molecular Therapeutics’ (4DMT) gene therapy candidate for the treatment of cystic fibrosis, 4D-710 demonstrated CFTR transgene RNA and protein expression in all 10 participants treated at the higher and lower doses with up to 12 months of follow-up in the Phase 1/2 AEROW clinical trial (NCT05248230).1 The data comes a few months after 4DMT announced it was gearing up for a pivotal Phase 3 trial and registration pathway for the 4D-710 therapy.

Data from the study were presented at the 47th European Cystic Fibrosis Conference in June 2024 in Glasgow, UK, by principal investigator Jennifer L. Taylor-Cousar, MD, MSCS, professor in the departments of medicine and pediatrics and co-director of the Adult Cystic Fibrosis Program and director of the Cystic Fibrosis Foundation Therapeutics Development Center, National Jewish Health.

CGTLive spoke with Taylor-Cousar to learn more about the progress of the AEROW study, the new data and the next steps of the study. She noted the higher than expected expression profile of the 2×10¹⁵ vg cohort and announced that the 1×10¹⁵ The VG dose was selected for the future. She expressed cautious optimism about the effectiveness of the therapy, having observed clinically meaningful improvements in lung function in at least one participant.

REFERENCES

1. 4DMT presents positive interim data from the Phase 1/2 AEROW clinical trial of aerosolized 4D-710 for modulator-unsuitable/intolerant cystic fibrosis at the 47th European Cystic Fibrosis Conference. Press release. 4DMT. June 6, 2024. https://www.cgtlive.com/view/4dmt-aligns-path-forward-cystic-fibrosis-gene-therapy-4d-710
2. 4DMT Announces Update on Regulatory Interactions and Development Pathway for 4D-710 for the Treatment of Cystic Fibrosis. Press Release. 4DMT. March 28, 2024. https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-announces-update-regulatory-interactions-and-development