#NACFC2022 — Trikafta for CF Shows Efficacy, Safety Across Ages

Poster shows results indicating medicine can benefit children as young as 2

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Treatment with Trikafta continues to be safe and well-tolerated, benefiting people with cystic fibrosis (CF) ages 12 and up who have been on treatment for almost three years. But benefits may also extend to children as young as 2.

That’s according to data that will be shared at this year’s North American Cystic Fibrosis Conference (NACFC), which is being held in Philadelphia.

CF occurs due to mutations in the CFTR gene, which codes for a protein of the same name. Deficient CFTR protein activity or levels impair the flow of chloride and water in and out of cells, resulting in an abnormally thick mucus buildup in certain body organs.

Trikafta is a triple combination therapy of elexacaftor, tezacaftor and ivacaftor, which together help CFTR fold correctly and hold it open so that more salt can pass through. These actions can help ease the symptoms of the disease.

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The medication, sold by Vertex Pharmaceuticals, was first approved in the U.S. in 2019 for people ages 12 and up who have at least one copy of the F508del mutation, which is the most common type of mutation causing CF. The approval was later expanded to cover more mutations and younger children.

CFTR modulators like TRIKAFTA have pivotally changed standard of care therapy in CF, and the CF community continues to benefit from ongoing collection and evaluation of long-term data,” Deepika Polineni, MD, professor of pediatrics and the director of the Cystic Fibrosis Center at Washington University School of Medicine in St. Louis, said in a press release.

NACFC studies on Trikafta

Polineni is one of the researchers in “Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least one F508del allele: 144-week interim results from an open-label extension study,” presented at the conference both as a poster and in an oral presentation.

The study (NCT03525574) is an open-label, 192-week extension of two Phase 3 clinical trials — called AURORA F/MF (NCT03525444) and AURORA F/F (NCT03525548) — that’s ongoing in CF patients 12 and up with at least one copy of the F508del mutation.

According to interim data cut at 144 weeks (almost three years), treatment with Trikafta keeps adding improvements to lung function and easing respiratory symptoms. The therapy was generally safe and well-tolerated, and most side effects were mild or moderate in severity.

“These long-term data at 144 weeks demonstrate remarkable health effects in the longest study of TRIKAFTA. The data show sustainment of the historic improvements in lung function, respiratory symptoms and sweat chloride, a marker of CFTR function,” Polineni said.

At the conference, another poster on pooled data from multiple Phase 3 clinical trials of CFTR modulators will circle back to the link between helping CFTR function closer to normal and achieving better outcomes in CF. The poster is titled “Greater Reductions in Sweat Chloride with CFTR Modulator Use are Associated with Improved Clinical Outcomes.”

According to the analysis, greater reduction in the level of sweat chloride, which can tell that the CFTR is working more actively, was linked to greater benefits to people ages 12 and up who were receiving treatment with CFTR modulators.

The benefits included better lung function, milder respiratory symptoms, and fewer episodes of worsening of symptoms or exacerbations, as well as higher body mass index (a measure of body fat). The best outcomes were seen in people who reached a level of sweat chloride less than 60 millimoles per liter.

“These new data add to the growing body of evidence demonstrating the benefits of our CFTR modulators across multiple clinical measures over the long-term, and the significant impact these medicines are having on patients,” said Carmen Bozic, MD. Bozic is Vertex’s executive vice president of global medicines development and medical affairs, as well as chief medical officer.

The company is also supporting an open-label, Phase 3 clinical trial (NCT04537793) that’s testing how well Trikafta works and how safe it is for younger children, ages 2–5, who have CF and two copies of the F508del mutation, or one copy of this mutation and another mutation of a minimal function — which results in a CFTR protein with minimal ability to function.

Data from 75 children who took part in this trial will be shared in the poster “A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 2 Through 5 Years of Age with Cystic Fibrosis and At Least One F508del Allele.”

Treatment with Trikafta led to a reduction in the level of sweat chloride, an improvement in lung function, and a stable nutritional status. It also was generally well-tolerated, with a safety profile consistent with that of older patients.

These findings suggest that treatment with Trikafta “has a favorable safety profile and provides clinically meaningful benefits in CFTR function to people with CF as young as 2 years of age,” the researchers wrote.

Based on these findings, Vertex recently filed a new drug application with the U.S. Food and Drug Administration to extend the use of Trikafta to children in this age range.

The company will also be filing for approvals with the European Medicines Agency and the U.K.’s Medicines and Healthcare products Regulatory Agency by the year’s end.

Note: The Cystic Fibrosis News Today team is providing in-depth coverage of the 2022 North American Cystic Fibrosis Conference (NACFC) Nov. 3–5. Go here to see the latest stories from the conference.

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