Real-world outcomes of generic elexacaftor/tezacaftor/ivacaftor (gETI) in South Africans (SA) with CF using standard versus clarithromycin-boosted gETI, modulator-sparing strategies to reduce cost.

Abstract

Objective: Access to highly effective modulator therapies (HEMT) in resource-limited countries is limited by prohibitive cost and restrictive patents. We report the clinical outcomes of a cost-reduction strategy in South Africa (SA), where generic elexacaftor/tezacaftor/ivacaftor (gETI) was pharmacokinetically enhanced with clarithromycin (gETI/c) for people with CF (pwCF) eligible for HEMT.

Methods: A multi-center observational study from December 2021 to May 2024. Analysis of variance (ANOVA) and linear mixed effects analyses were conducted to describe and compare change in sweat chloride (SC), FEV1pp, BMI (m/kg²) and adverse events (AE) over 18-months follow-up for different gETI dose categories: a) standard, full or b) modulator sparing dose (gETI/c at 25-50 % recommended dose, twice/thrice weekly).

Results: 70/413 (17 %) eligible pwCF [median age 27 years (range 6-52); 68 (97 %) with ≥ one copy F508del] received gETI with standard (n = 38) or modulator-sparing doses (n = 32); 29 changed dosing regimens across the study period. The overall mean (SD) reduction in SC after 1-month of treatment was -52.9 (16.9) mmol/L (p < 0.001), with no evidence of difference between dose groups (p = 0.2). Overall mean (SD) FEV1pp and BMI increased at 1-month by 14.9 (95 % CI 11.49-18.40) and 0.84 (95 % CI 0.16-1.49), respectively. Improvements in FEV1pp and BMI were sustained throughout follow-up, with no evidence of difference between dosing groups. No serious AEs were reported.

Conclusion: Our experience with gETI is similar to real-world reports using the originator product. Boosting ETI with CYP3A-inhibitors is a safe and effective strategy to increase access to ETI in settings where access to HEMT is restricted.