A new drug regimen is safe and effective in children with cystic fibrosis

A Level 3 open-label international study, co-led by Susanna McColley, MD, of Ann & Robert H. Lurie Children’s Hospital in Chicago, found that a regimen of three drugs (elexacaftor / tezacaftor / ivacaftor) that aimed at the genetic cause of safe and effective cystic fibrosis in 6-11-year-old children with at least one mutation of F508del mutation in the CFTR gene, which is estimated to represent nearly 90 percent of the cystic fibrosis population in the United States.

For children in this age group who have only one copy of the F508del mutation – or about 40 percent of patients with cystic fibrosis in the United States – this was the first treatment to address the an underlying genetic defect in cystic fibrosis.

This tri-drug cystic fibrosis treatment was approved by the FDA in October 2019 for people 12 years and older with at least one copy of the F508del mutation. Based on the positive results of this study, the FDA has accepted the application to extend treatment signal to younger children, with a decision expected by June 2021.

“What is most interesting about our findings is that this population of children had normal lung function at the start of the study and was still developing significantly,” said Dr McColley, Chief Consortium. on the study and senior author, former Scientific Director for Interdisciplinary Research Partnerships at Lurie Children’s Stanley Manne Children’s Research Institute and Professor of Pediatrics at Northwestern University’s Feinberg School of Medicine. ”Along with what we saw in studies and in used with the older population, earlier onset of treatment could avoid serious long – term complications and alter the health pathway for children with cystic fibrosis. “

Cystic fibrosis is a progressive genetic disease that damages several organs, including the lungs and pancreas. Currently, the average life expectancy is 47 years. The disease is caused by mutations in the CFTR gene that lead to insufficient flow of salt and water in and out of cells. In the lungs, this creates a buildup of thick, sticky mucus that can cause harmful lung diseases and severe lung disease. Damage to the pancreas occurs even before birth, which inhibits the uptake and growth of nutrients. Although there are about 2,000 known mutations of the CFTR gene, the most common is the F508del mutation.

In the 24-week study with 66 children, published in the American Journal of Respiratory Care and Emergency Care Treatment, Dr. McColley and colleagues confirmed the suitability of a dose that is half the adult daily dose of the drug treatment for 6-11 year olds weighing less than 30 kg and the full adult dose for those with higher weight greater. The regiment was well received, and the safety profile was consistent with those seen in elderly patients, with cough, headache and fever being the most common adverse events.

The treatment significantly improved lung function, respiratory symptoms and nutritional status. Maintenance or improvement of nutritional status is associated with improved lung function and increased survival in patients with cystic fibrosis. In addition, a significant improvement in sweat chloride density, a direct measure of CFTR function, was observed.

In this study, we observed greater improvements in sweat chloride than those previously seen in adults and adolescents. This strong response to treatment may lead to improved long-term clinical outcomes of cystic fibrosis. “

Dr. Susanna McColley, Senior Study Author and Chief Combined Investigator, Ann & Robert H. Lurie Children’s Hospital in Chicago

“It is important to note that people with cystic fibrosis who are demographically identified as race rather than white or ethnic are identified as Hispanic are less likely to have an F508del mutation,” Dr. McColley said. “This is important because as with other serious and debilitating illnesses, these numbers have more severe disease and lower life expectancy. As drug development continues, we are focusing on treatment or treatment. very effective for everyone with cystic fibrosis. “