Gains in nutrition, growth seen for young CF children starting Orkambi

Small real-world study shows benefits of treatment in first 6 months

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Among young children with cystic fibrosis (CF), starting the approved oral therapy Orkambi (ivacaftor/lumacaftor) led to favorable changes in nutrition and growth status during the first six months of treatment, according to a small real-world study.

Orkambi, first approved in the U.S. in 2015 and now indicated for patients as young as 1 year, was designed to treat CF caused by the F508del mutation in the CFTR gene — the most common disease-causing mutation. Called a CFTR modulator, Orkambi’s active ingredients, lumacaftor and ivacaftor, are designed to correct defects in the production and function of the CFTR protein due to an F508del mutation.

While the therapy has been shown to prevent the buildup of the thick and sticky mucus that’s a hallmark of CF, little was known about its effects on nutrition and growth, especially in younger patients.

“These data contribute to the understanding of CTFR modulators and their effects on metabolic processes and digestion,” the scientists wrote.

The new findings were detailed in a study titled “Impact of lumacaftor/ivacaftor on nutrition and growth in modulator-naïve children over 24 weeks,” published in the Journal of Cystic Fibrosis.

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Seeking data on effects of Orkambi on underlying mechanisms of growth

To date, the therapy’s use has shown certain benefits in CF children ages 2 to 5 who have two copies of F508del. In a Phase 3 open-label extension trial (NCT03125395), more than two years of treatment with Orkambi in this patient population was found to improve outcomes such as sweat chloride, pancreatic function, and growth.

However, limited real-world data exist on outcomes related to nutrition and the underlying mechanisms of growth changes among CF children who are just beginning Orkambi.

“Achieving and maintaining normal weight, stature and [body mass index] early in life, particularly during this period of rapid growth is of paramount importance,” according to the team, led by scientists at the Children’s Hospital of Philadelphia, in Pennsylvania.

Thus, to determine the effects of Orkambi in more detail, the researchers conducted an observational study (NCT03795363) that enrolled children from CF centers in the U.S. and Canada. These children, ages 2 to 5.9 years, had never received Orkambi.

The team collected data before treatment, and after 12 weeks, or about three months, and 24 weeks, or almost six months, of starting Orkambi. These data included body measurements, diet, energy expenditure, pancreatic status, and biomarkers for nutrition and inflammation.

Of the 28 children initially enrolled, 18 completed the 12-week follow-up, and 21 attended the 24-week follow-up.

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Children ages 2-5 experience weight-for-age gains with treatment

The results showed that so-called weight-for-age scores significantly increased at both 12 and 24 weeks.

Increases in weight-for-age “remained within a range typical for growing children, indicating there was not a shift to overnutrition,” the researchers wrote.

Head circumference-for-age scores also increased significantly by 12 weeks but not at 24 weeks. Another test measuring body fat showed significant improvement at 24 weeks only.

Lab tests showed lower blood carbon dioxide levels at 24 weeks, a sign of improved lung function, and higher creatinine, a waste product from the digestion of protein. Serum total bile acids, particularly chenodeoxycholic acid and cholic acid, which help with digestion, also increased at 24 weeks. Fecal calprotectin, a marker for gut inflammation, decreased at 12 and 24 weeks.

In summary, [the data] showed improvements in nutrition and growth status among young children initiating [Orkambi] therapy after 24 weeks.

Regarding fatty acids, two essential omega-3 fatty acids, called alpha-linolenic acid and docosahexaenoic acid, significantly decreased at 12 and 24 weeks, while mead acid, an omega-9 fatty acid, significantly increased.

“While some of the changes in these fatty acids were statistically significant in the current study, all of the fatty acids remained within the reference range,” the scientists wrote, adding, therefore, “we suggest that these CFTR modulators did not have positive effects on [polyunsaturated fatty acids] and specifically [essential fatty acids] status during the intervention period.”

Participants had normal mean resting energy expenditure, as measured by kcal/day, before treatment, and there were no significant changes after starting the therapy. Nor were there significant changes in energy intake (kcals) and the percent estimated energy requirement, which estimated total energy requirements based on age, sex, weight, height, physical activity, and food intake.

Parents reported adherence to Orkambi at rates ranging from 85% to 100%, as averaged from weeks four, 16, and 20. CF-specific vitamins varied from 43% to 100%, and pancreatic enzymes from 71% to 100%.

“In summary, [the data] showed improvements in nutrition and growth status among young children initiating [Orkambi] therapy after 24 weeks,” the scientists concluded.

This work was partially supported by an Investigator Initiated Program award from Vertex Pharmaceuticals, which markets Orkambi, as well as an award from the Cystic Fibrosis Foundation.