A life-changing drug: Patients see improvement of cystic fibrosis symptoms
BY AMBER SMITH
Brittnee Farmer, 31, is planning her wedding. She worries that the big day will be marred by her nebulizer, the machine she uses to inhale medication in a fine mist.
Farmer was a preschooler when she was diagnosed with cystic fibrosis. Because of the genetic disorder, thick mucus accumulates in her lungs, causing Farmer to cough — and to seek relief from her nebulizer.
She really wants to enjoy her wedding day without the machine.
She gets teary-eyed now, thinking that may be possible.
Farmer is one of the first cystic fibrosis patients at Upstate to start taking a newly approved CF medication for those age 12 and older called Trikafta. Within the first two weeks on the regimen — two pills in the morning and one at night — Farmer no longer feels short of breath when she awakens in the morning. She no longer jumps out of bed to run to her nebulizer.
“It’s like I got a new body,” she says. “It’s like I returned a defective one and got a new one.
“It’s very much a life-changing drug for me.”
It’s the first therapy that successfully targets the genetic root of CF rather than just alleviating symptoms.
Christopher Fortner, MD, PhD, medical director of the cystic fibrosis program at Upstate, says one of the first things patients notice when taking the new drug is an improvement in how they feel. “Most of them told me they coughed out a lot of mucus the first few days after starting Trikafta, but then their cough went almost completely away,” he says. “For some of them who have coughed almost every day they can remember, this is a huge improvement.”
He says during clinical trials of Trikafta, patients completed surveys that gave symptom scores based on mucus production, congestion, cough, wheezing and shortness of breath. This score improved by about 20 points for people who had never taken a modulator before. Symptoms improved, and so did their measurable lung function and the amount of chloride in their sweat.
Trikafta is not a cure for CF.
If patients stopped taking the drug, Fortner predicts their mucus would become thick again, their cough would return and their lung function would drop. “But taking Trikafta as directed by their CF doctors will help their CF protein work much better and may minimize both the symptoms of CF and the progression of the disease.”
The hope is that Trikafta can help turn CF into a chronic disease, like diabetes.(Hear Christopher Fortner, MD, PhD, describe the promise of the cystic fibrosis drug Trikafta in a podcast interview with Upstate's "HealthLink on Air.")
The life expectancy for someone born with CF today is, on average, 44 years. Trikafta could change that. “I think it’s going to improve the life expectancy by a lot,” says Fortner. “It could really have a dramatic improvement not just for how long they’ll live, but for living more days without symptoms and feeling better.”
That’s been Farmer’s experience since starting Trikafta in November.
Farmer met her fiancé on a Myrtle Beach vacation. Their romance continued long distance until Farmer moved from Charlottesville, Va., to be with Brian Cooney near Utica. Her move meant finding new doctors.
“My first appointment at Upstate, I felt more comfortable than I ever had with my team in Virginia, and I had been there my whole life,” she says. She told her doctor, “I feel like I am just getting my diagnosis. There is so much that you are telling me that I did not know.”
She was 4 when she was diagnosed, but she remained active, playing with cousins, competing on the swim team, cheerleading. Her mom and dad helped her learn how to live with her condition, but Farmer says, “It was never really like a disability. I didn’t share the fact that I had CF with a lot of people, just because I wanted people to know me.”
She coughed a lot. She used a nebulizer first thing every morning, and throughout the day. She took enzymes before meals to help her body absorb nutrition.
She heard about a new medication in development that could, potentially, improve the lives of people with CF, but she did not get her hopes up.
Then, when she relocated to Central New York and began receiving care at Upstate, she learned she was a candidate for the drug that has changed her life.
Farmer and Cooney plan to be married in October. And Farmer doesn’t expect to need her nebulizer to get through the day.
To understand how the new CF medication works, you first have to understand the role of the cystic fibrosis transmembrane conductance regulator protein, or CFTR protein. This protein forms a tiny channel, or tube, that allows chloride to flow across the cell membrane, allowing water to move from one side of the cell layer to another. Without this protein, sweat is too salty, mucus in the airways is too thick and sticky, and similar problems occur in the pancreas, intestines and sinuses.
About 90% of CF patients have at least one CFTR genetic mutation, which causes problems in the channel formation. The protein doesn’t fold correctly into a tube; the cells reject that misfolded protein and won’t send it up to the top of the cells, where it needs to be in order to let chloride move across the membrane.
Two of the ingredients in Trikafta help the protein fold well enough to form a tube. But even if the protein folds into a good enough tube to be sent to the cell surface, the ends of the tube are closed and won’t let chloride through. The third ingredient in Trikafta helps keep the tube open.
“With these three ingredients working together, the CF protein works better, but still not as good as a CF protein with no mutations,” explains Christopher Fortner, MD, PhD, the medical director of the cystic fibrosis program at Upstate.
Trikafta is not designed to treat people with CF who do not have a CFTR mutation. Fortner notes that a huge research push is underway to find therapies for those patients.
This article is from the winter 2020 issue of Upstate Health magazine.