TOPLINE

In a real-world study of patients with cystic fibrosis (CF), 12 months of treatment with a generic formulation of elexacaftor-tezacaftor-ivacaftor (ETI) improved lung function and quality of life, lowered sweat chloride concentrations, and reduced severe respiratory exacerbations, with the treatment being generally well tolerated. 

METHODOLOGY

• Researchers conducted a prospective, observational study (July 2022-June 2024) at a single center in Argentina to evaluate the efficacy and safety of a generic ETI formulation in 71 patients with CF who had responsive gene variants.
• They assigned 43 patients (median age, 10.9 years; 55.8% female) who had never received treatment with a CF transmembrane conductance regulator modulator to the treatment-naive group and 28 patients (median age, 10.6 years; 25% female) who had received treatment with lumacaftor-ivacaftor for more than 1 year to the previously treated group.
• Patients aged 6-12 years and/or weighing < 30 kg received two tablets of ETI (50 mg elexacaftor, 25 mg tezacaftor, 37.5 mg ivacaftor) in the morning and 75 mg ivacaftor at night. Patients older than 12 years and weighing > 30 kg received two tablets of ETI (100 mg elexacaftor, 50 mg tezacaftor, 75 mg ivacaftor) in the morning and 150 mg ivacaftor at night.
• Outcome measures included lung function (percent predicted forced expiratory volume in 1 second [FEV1] and lung clearance index), nutritional status (BMI z-score), respiratory quality of life, sweat chloride concentrations, fecal elastase levels, liver enzyme levels, and severe pulmonary exacerbations. 
• Patients were followed up every 3 months for up to 12 months, with measurements for sweat chloride concentrations performed only at baseline and months 3 and 12 and for fecal elastase performed only at baseline and month 6.

TAKEAWAY

• After 12 months, median percent-predicted FEV1 improved by 20.8% in the treatment-naive group and by 18.5% in the previously treated group (P < .01 for both), with no significant difference between the groups.
• By month 12, lung clearance index decreased by 13.3% in the treatment-naive group and by 11.2% in the previously treated group (P < .05 for both), with no significant difference between the groups. Severe pulmonary exacerbations were substantially reduced in both groups.
• From baseline to month 12, sweat chloride concentration decreased by 53.1% in the treatment-naive group and by 58.2% in the previously treated group (P < .01 for both), with no significant difference between the groups. BMI z-score increased in treatment-naive patients (P < .001), whereas previously treated patients showed a nonsignificant increase.
• Fecal elastase levels showed no clinical relevance. Adverse events were mostly mild: Elevations in transient liver enzyme levels occurred in five patients and rashes occurred in three patients, with one patient with rash requiring temporary discontinuation of the ETI therapy.

IN PRACTICE

“[The] results confirm that treatment with generic ETI is as effective as non‐generic formulations and shine a spotlight on the possible cost benefits and improved accessibility of effective treatments for pwCF [ people with CF], who remain with restricted access in many parts of the world ,” the authors of the study wrote.

SOURCE

This study was led by Alejandro Teper, Ciudad Autónoma de Buenos Aires, Argentina. It was published online on June 16 in Pediatric Pulmonology.

LIMITATIONS

This study was conducted at a single center. The trial did not include a comparator group treated with an alternative triple therapy. Data on pharmacokinetics were not obtained. 

DISCLOSURES

The authors did not report any funding information and declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.