New research published in The Lancet Respiratory Medicine journal reports that the oral drug ivacaftor is a safe therapy and has the potential to benefit young children between the ages of 2-5 who suffer from a specific type of cystic fibrosis (CF). Scientists said there may be a possibility of mitigating organ damage early in life with the drug.
Cystic fibrosis is an incurable disease caused by a defective gene that progressively damages the lungs and digestive system. The genetic defect disrupts the cystic fibrosis trans-membrane conductance regulator (CFTR) protein activity which regulates salt transport in cells, causing a buildup of a thick, sticky mucus in the lungs and digestive system, leading to infections and untreatable lung damage.
Current estimates are that that 10,000 people live with cystic fibrosis in the United Kingdom alone, with more than 70,000 suffering from the disease worldwide.
Ivacaftor works by targeting the basic defect of CFTR, present in about 4 percent of CF patients with at least one mutation in the CFTR gene. Previous research showed the drug to be a safe and effective treatment in children starting at age 6, teenagers, and adults, with the so-called “gating” mutations (KIWI) in CFTR.
Ivacaftor has already been approved as a therapy for those age groups. Now, researchers conducted the first study to examine the drug’s effects in younger children.
The clinical trial enrolled 34 preschoolers with CF between 2-5 years old, with at least one copy of a CFTR gene mutation. The findings showed that taking the oral drug twice a day for six months at one of two doses – 50 mg for children weighing less than 31 pounds and 75 mg for children weighing more than that – considerably improved several markers of disease, including sweat chloride levels, pancreatic function and weight gain.
Ivacaftor received no reports of intolerability and achieved a safety profile close to that seen in adults. The most commonly reported adverse effects were cough in 19 children (56 percent) and vomiting in 10 children (29 percent). Five children (15 percent) tested liver function (LFTs) eight times above the normal limits, and one of them consequently stopped the treatment.
The 33 children who reached the end of the six-month treatment experienced considerable reductions in sweat chloride levels – suggesting an improvement in their own bodies’ ability to restore the salt balance in and out of cells (when defective, this is the process that leads to CF) – and improved weight gain, which could provide a buffer against the decline in nutritional levels and improved lung function later in childhood.
Furthermore, more than a quarter of the children surpassed the clinical cut-off for pancreatic insufficiency at least one time during treatment, which suggests that “a window in early life where at least partial restoration of pancreatic function might be possible,” the authors wrote in a press release. This appears promising because it is the first time it was ever observed with any drug in CF patients.
The study authors cautioned, however, that more data is necessary to confirm the effects and safety of long-term treatment.
“This was a small trial, but we are thrilled to see these results,” said Prof. Jane Davies of the National Heart and Lung Institute at Imperial College London, who led the investigation. “Ivacaftor is a potential new treatment to offer children age 2 and older with cystic fibrosis and a CFTR gating mutation. This novel therapy could substantially impact these children’s lives, potentially opening the way to even greater progress in years to come.”
“Davies and colleagues’ study is groundbreaking for cystic fibrosis care in children aged 2-5 years,” wrote Sophie Yammine and Philipp Latzin from University Children’s Hospital Bern in Switzerland and Florian Singer from University Children’s Hospital Zurich. “Targeted treatment of this basic defect has potential for both prevention of damage and functional improvement of affected organs.
“Ivacaftor is safe, and results of secondary outcome measures suggest efficacy in this age group that is similar to that in older patients,” they wrote. “Many unknowns remain, however, such as the earliest age of possible application, data for natural fluctuation of new outcome variables, and other points that have been reviewed previously. In any case, the results published by Davies and colleagues are good news for young children with cystic fibrosis and their families, who often have an insufficient amount of advocacy.”