Triple Combination Therapy Improves Lung Function in Cystic Fibrosis

November 2, 2019

A 3-drug combination of elexacaftor, tezacaftor, and ivacaftor may benefit patients with cystic fibrosis with Phe508del-minimal function genotypes, in whom previous cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimens have been ineffective, according to a study published in The New England Journal of Medicine.

Earlier this month, the Food and Drug Administration approved the therapy based on the results of this international study.

“Although there are over a thousand different disease-causing mutations, nearly 90% of people with cystic fibrosis have at least 1 copy of the most common mutation, the Phe508del CFTR allele,” said Raksha Jain, MD, University of Texas Southwestern Medical Center, Dallas, Texas.

“This 3-drug combination was highly effective in people with cystic fibrosis who inherited the Phe508del CFTR mutation, improving health outcomes and symptoms,” she added.

For the study, Peter Middleton, MD, University of Sydney, Sydney, Australia, and colleagues analysed 403 patients aged ≥12 years with cystic fibrosis with Phe508del–minimal function genotypes. The patients were randomised to receive either elexacaftor-tezacaftor-ivacaftor combined therapy or placebo for 24 weeks. The researchers compared lung function in patients at 4 and 24 weeks.

The study found that compared with placebo, treatment with elexacaftor-tezacaftor-ivacaftor resulted in a percentage of predicted forced expiratory volume in 1 second that was 13.8 points higher at 4 weeks and 14.3 points higher through 24 weeks. In addition, lung flare-ups were 63% lower in the treatment group. On questionnaires regarding their quality of life and respiratory symptoms, patients who took the 3-drug combination reported higher scores in these areas.

The treatment group also had a lower concentration of salt in their sweat than the placebo group, which demonstrates how this therapy targets the underlying cause of the disease, noted Dr. Jain.

Elexacaftor-tezacaftor-ivacaftor was generally safe and had an acceptable side effect profile. Most patients had adverse events that were mild or moderate. Adverse events leading to discontinuation of the trial regimen occurred in 1% of the patients in the elexacaftor-tezacaftor-ivacaftor group.

“The cystic fibrosis community is working hard to find highly effective therapies for people who are not eligible for this treatment because they do not have the appropriate gene mutation,” concluded Dr. Jain.

Reference: http://dx.doi.org/10.1056/NEJMoa1908639

SOURCE: UT Southwestern Medical Center