Investigating Breakthrough Cystic Fibrosis Drug's Effect on Weight

A new project at The Children’s Hospital of Philadephia seeks to gain a clearer idea of what effect the novel cystic fibrosis drug ivacaftor has on energy balance and weight gain. With the support of the drug’s manufacturer, Vertex Pharmaceuticals, CHOP’s Virginia A. Stallings, MD, will measure the degree to which patients with cystic fibrosis taking ivacaftor — which is sold under the name Kalydeco — experience improvements in nutritional status and growth.

An inherited disease that is chronic, progressive, and often fatal, according to the Cystic Fibrosis Foundation cystic fibrosis affects approximately 30,000 adults and children in the United States and 70,000 worldwide. The disease is characterized by thick mucus that causes respiratory and digestive issues, and is associated with poor growth and weight gain, among other complications. There is currently no cure for cystic fibrosis, and until recently most treatments have focused on alleviating the disease’s symptoms.

Kalydeco is approved to treat CF in patients 6 years of age and older who have specific mutations in their cystic fibrosis gene. Kalydeco was first approved in 2012 on the strength of trials that showed it improved lung function “and other aspects of cystic fibrosis such as increasing weight gain,” according to the FDA. Though the FDA recently expanded the number of mutations for which Kalydeco is approved, because its approval is restricted to particular mutations it can currently only treat a small segment of the overall cystic fibrosis population. Nonetheless, Kalydeco is a “breakthrough” drug, said CHOP’s Dr. Stallings.

With this project, Dr. Stallings will examine Kalydeco’s effect on cystic fibrosis patients’ energy balance and weight gain. Dr. Stallings and her team proposed the study to Vertex after noting the unexpected weight gain observed during Kalydeco’s clinical trials.

Much of Dr. Stallings’ career has been spent working on ways to improve cystic fibrosis patients’ weight and growth, so the approval of Kalydeco — which treats the “primary cellular defect” — was “was a major, exciting, proof-of-principle,” she said.

“What caught our eye with this is as they were doing the clinical trials there was a completely unexpected weight gain … almost every participant was gaining weight,” Dr. Stallings noted.

She proposed a comprehensive study that will investigate what effect Kalydeco has on pancreatic function, how well patients are able to absorb food, and whether taking the drug has any effect on the patients’ appetite and food intake. Over the next 18 months, Dr. Stallings and her team will enroll patients who are about to go on the drug, to measure the effect Kalydeco has on their weight, appetite, and energy intake and needs before, during, and after treatment. The study will make use of innovative “SmartPills” that can measure changes in pH and gastrointestinal motility, Dr. Stallings said.

In a related project supported by the Cystic Fibrosis Foundation, Andrea Kelly, MD, from the Division of Endocrinology and Diabetes, has been working on an investigation of Kalydeco’s effect on insulin and insulin secretion. If the investigators were able to compare findings (not to mention share study participants), “we would have a spectacular look at the whole metabolic change,” said Dr. Stallings.

Saying she was excited about the study, and the promise of novel therapies like Kalydeco, Dr. Stallings said, “we’ve never had a time in CF when we could almost guarantee weight gain … so here we have an experimental design where almost everybody is going to gain weight.”

To learn more about cystic fibrosis, and cystic fibrosis research at The Children’s Hospital of Philadelphia, see the Cystic Fibrosis Center website.