Caleb Nolan, 10, ducks past his 8-year-old sister Haley and drives the court: a layup ricochets off the backboard and misses the hoop. Caleb snaps up the falling ball and drives the other way, tries again.
Caleb lives and breathes basketball. His basketball card collection numbers in the hundreds; he can rattle off player statistics on demand. His mom, Melissa Nolan, looks on as he heads back down the court. “He’ll do this all day.”
Which isn’t so incredible in itself. What’s incredible in Caleb’s case is that Caleb has cystic fibrosis (CF).
“There are over 1,900 known genetic mutations and variants in cystic fibrosis, and each is linked with a particular abnormality in the protein,” says Scott Sagel, MD, PhD, Caleb’s primary CF physician. “Caleb’s particular mutation, among the ten most common mutations in the US, leads to a gating abnormality, where a protein is supposed to function as a channel for salt. The protein doesn’t gate properly, so it doesn’t move salt.”
The consequence of that blockage is mucus. It builds up in the lungs, the sinuses, the pancreas. Food doesn’t absorb, the lungs clog. It’s difficult to breathe. All that mucus is also an ideal breeding ground for bacteria, leading to frequent infections. Caleb’s initial prognosis: an average of 14 days in the hospital every six months.
“I was so afraid of germs,” Melissa recalls. “I felt like he was going to be the boy in the bubble.”
Still, Caleb did reasonably well on a combination of 30-some enzymes daily, several multivitamins and a few hours a day in a vibrating vest designed to loosen mucus in the lungs. It wasn’t ideal, but Caleb managed a few years with no hospital stays.
Then came Orkambi.
“When I got it, I was like, ‘Oh, another med’,” says Caleb. “But then it changed my life.”
“This is the first drug approved by the FDA that targets the genetic defect of CF, which is that protein abnormality,” says Dr. Sagel, who served as the lead site investigator for the multicenter Phase II trial of Orkambi, better known by its trade name, Kalydeco. Children’s Colorado’s team includes some of the world’s foremost CF experts. The trial was held at our Mike McMorris Cystic Fibrosis Research and Care Center, which proved Orkambi to be safe and effective.
The drug works as stand-alone therapy for people with Caleb’s mutation and certain other rare mutations — currently about 8% of the CF population. In 2015, Orkambi in combination with another protein rescue treatment was approved for children age 12 and older with two copies of the most common CF mutation, F508del. More than 10,000 people living with CF will benefit — out of about 70,000 worldwide.
A complete 180
For Caleb, the result has been “a complete 180,” Melissa says. His nutrient absorption and lung function improved, and he went from three hours a day in the vest to just one. He was less tired and got sick less often. His fourth-grade school attendance record was perfect.
Best of all: he plays on a basketball team — and he’s good. “If you’d told me a couple years ago Caleb would be playing basketball competitively,” Melissa says, “I would have said you were crazy. I probably wouldn’t even have let him.”