Trikafta: New drug provides hope for cystic fibrosis patients
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Trikafta: New drug provides hope for cystic fibrosis patients

Jeffrey and Sarah Yourman
Jeffrey and Sarah Yourman

I first met the siblings Sarah and Jeffrey Yourman almost 10 years ago, when they were suburban teenagers growing up in Fair Lawn.

They were not typical teens, however. They were dealing with a devastating legacy — they both inherited a genetic disease, cystic fibrosis. Back then, a new drug was being tested for CF, and both youngsters took part in Phase III trials designed to test if the drug could overcome the genetic malfunction, a defective or missing transport protein called CFTR. To their dismay, that drug did not prove to be the panacea that doctors and parents had hoped it would be, and the experimental trials were discontinued.

Researchers continued to seek answers for CF patients, though, and now a new drug, Trikafta, is available. It appears to be very promising. Sarah and Jeffrey are hopeful again, and within days of starting the drug, they both have experienced dramatic improvements in health. “It’s a game-changer,” their mother, Lisa Yourman said. “This is the biggest game changer we’ve ever had.” She reported that there has been “an amazing change to their health outcomes within 48 hours of starting Trikafta and, as we say, ‘not a cough in the house.’”

Lisa Yourman has spent the last 28 years learning about cystic fibrosis, advocating for CF patients, and investigating every therapy that offered relief for Sarah and Jeffrey. She scrutinized every new development related to CF, hoping to give her children a more normal life, a life of hope, and a real future.

Jeffrey Yourman, who just turned 27, graduated from Kean University. He is a software developer. His sister Sarah Yourman, 29, who has both CF and CF-induced diabetes, is a registered dietician working for credentials as a diabetes educator, and she is engaged to be married. Despite their daily regimen of complex therapies, drugs, and treatments, punctuated with medical crises, the siblings had as normal a childhood as possible. They are both active, they enjoy adventurous and rigorous sports, such as skiing, basketball, and hiking, and they have busy professional lives. This is no mean feat for CF patients, who typically spend hours every day on medical therapy and may experience unpredictable medical crises.

Cystic fibrosis is a genetic disease that is caused by a missing or defective protein called CFTR, (cystic fibrosis transmembrane conductance regulator protein). The normal version of the protein moves water and salt in and out of cells in the lungs, digestive system, and other vital organs. Most people are born with two functional copies of the CFTR gene. A person who has one functional copy and one flawed, mutated copy of the gene is called a carrier. When two people who are carriers conceive a child, there is a one-in-four chance that their child will inherit two copies of the mutation and have the disease.

Sarah Yourman was a toddler when she was diagnosed with CF. By then, Lisa and Steven Yourman already were expecting their second child, Jeffrey, who was diagnosed with the disease shortly after birth.

Taking care of the children’s medical needs was a formidable challenge. Sarah and Jeffrey’s lives were dependent on rigorous and consistent therapies and medications. They both had to endure daily regimens of chest physical therapy, a process in which a physical therapist drums on the child’s chest and back to dislodge the mucus clogging the lungs and thus help the child to breath. Both children needed antibiotics, growth hormone, pancreatic digestive enzyme capsules, and daily nebulizer treatments. For most of their lives, Sarah and Jeffrey also have used a novel device, an automated vest that vibrates; the oscillations loosen the mucus to clear their air passages. As adults, they still don their vests every day for a period of time in the morning or at night (and sometimes both), and they use a nebulizer to apply medications to their lungs.

Over the years, there have been other drugs that seemed promising but did not yield much success. But Lisa is confident this development is different. “We were always hopeful that something would come in their lifetime to enable them to stay healthy,” she said. “This is a momentous occasion. Thirty years after finding the gene, it is coming to fruition.” She explained that the CF gene was first identified in 1989, opening the door to understanding the mechanism of the disease.

When the CFTR protein is missing, that can lead to many complications in a growing child and adult. The most life-threatening complication is the accumulation of mucus in the lungs that disrupts normal breathing. The defective protein also leads to digestive issues, affects growth, and causes infertility in most CF males. Not too long ago, a diagnosis of cystic fibrosis doomed patients to a short life filled with many medical complications, and an average life expectancy in the teens. But CF survival has been steadily and dramatically increasing; average life expectancies now are in the 40s, and many CF patients live much longer, with a high quality of life.

Sarah and Jeffrey Yourman with their inhalers.

The new drug Trikafta, made by Vertex Pharmaceuticals, is a combination of three drugs that help the defective CFTR protein do its work. The drug works only in patients who have the mutation known as F508del. Of the 70,000 CF patients worldwide — about half of whom live in the United States — 90 percent have at least one copy of the F508del mutation. That’s good news for most CF patients, as this new drug facilitates the movement of CFTR protein to the surface of the cell and helps it transport materials through the membrane.

The CFTR gene can have many variations, but not all of them cause disease. Genetic testing can reveal the presence of the most common mutations associated with CF. The Cystic Fibrosis Foundation (www.cff.org) reports that about 1 in 35 Americans (about 10 million people) are carriers who have one copy of the mutation. In the Ashkenazi Jewish population, the carrier rate is 1 in 26. The top three most common mutations found in the Ashkenazi Jewish population are W1282X, F508del, and G542X. While Trikafta targets F508del (the defect present in most CF patients), it will not work in people with two copies of other mutations.

Lisa explained that Sarah and Jeffrey have one copy of the most common mutation, F508del, so they can benefit from the drug. Their other copy of the gene is the “nonsense mutation” known as G542X.

Lisa, who now is a divorced single mother, learned how to navigate and negotiate complex health insurance issues on behalf of her children. This was critical because the medical care, including therapies, drugs, and doctors, is extremely expensive. The new drug costs $26,000 a month, or $312,000 per year. Fortunately, her children’s health insurance will cover most of the cost. Lisa said that Jeffrey will pay about $5,550 and Sarah will pay about $7,900 per year for Trikafta. “Without it, Sarah would be going on antibiotics and prednisone,” and would be likely to experience more serious health complications, Lisa said.

Sarah Yourman started taking Trikafta at the beginning of November, and she reports remarkable success. “I didn’t have the ‘big purge,’” said Sarah, referring to reports that some patients experience dramatic clearing of the mucus. “But for me, I just stopped coughing. I still clear my lungs a little, but nothing like what I had to deal with. For me it’s a huge change. It’s just nice not to cough. I’ve just felt really good.

“I still have CF, so I’m still treating it as I normally would,” she added. “I still do the vest, and still take my enzymes and vitamins. But because I was so sick, I was losing weight. I’ve started to put on weight, as I’m absorbing more nutrients from my food.”

Sarah also reported that symptoms of inflammation that had plagued her have been reduced. Most noticeable is that her rosacea (a red face rash) is much improved. The process is not difficult, she said. She takes two pills in the morning and one pill at night, together with food containing some fat.

Lisa reported that the FDA approval for Trikafta originally was scheduled for March 2020, but it showed such promise that the agency fast-tracked its approval, moving the date up so patients could be treated sooner. “I even think Vertex was surprised,” said Lisa, referring to the company that developed the drug. On November 1 the scientific studies were presented at the 33rd annual North American Cystic Fibrosis conference, and the results of the experimental trials were published concurrently in two prestigious journals, the Lancet and the New England Journal of Medicine.

Sarah explained that she typically has gotten infections two or three times a year, requiring IV antibiotics. She also knows CFers, as they are called, who must undergo treatments three to four times a day. She hopes that with this drug, she and others like her will be healthier and able to cut back on treatment regimens.

“I think it gives you more hope for the future and lets you lead a more normal life,” Sarah said. “I always led a normal life, but I always coughed a lot. It’s weird not to cough. I’m able to lead a more normal life.

“I still ski. I took up running, but I broke my ankle in April, so I’m doing my first run post ankle breaking on Thursday. I do fun runs. My goal is just to finish.”

There are a lot of factors that determine the severity of cystic fibrosis. Jeffrey is what his mother calls a “healthy CFer,” who wanted to wait for others to get the drug before him. “He’s been very healthy,” Lisa said. “Boys always do better than girls, because of estrogen. In 2013 we started Sarah on shots that lowers the estrogen, and she’s done better since.”

Jeffrey started treatment with the new drug at the end of November, and he reports being pleasantly surprised. “Honestly, I wasn’t expecting it,” he said. “I feel the best I have in years. I’ve always been pretty healthy, and only had one true PICC line,” the catheter used for IV antibiotics. “I thought I would need one, but the doctor said ‘just start the drug,’ and now I don’t need one. Just two pills in the morning and one at night, taken along with food containing 8 to 10 grams of fat.”

“I’m happy for her,” Jeffrey said of his sister. “She’s always been relatively sick throughout her life. It’s great to see her happier and healthier.”

He voiced concern over the new drug’s cost and availability. “The drug is only for people who have a specific mutation in the CFTR gene. It worked for me, and I hope that people who have the same mutation can get it.

“I’m sure they will be coming out with more drugs too,” he continued; however, “This drug isn’t cheap, and that’s not fair. It’s ridiculous that pharmaceutical companies can charge so much for a drug. These types of drugs everybody should be able to be on, insurance or not.”

“They’ve overcome a lot of adversity,” Lisa said proudly of her children. “They do the best they can. They’re very positive thinkers. For people who have CF to be in the workforce is amazing.

“They still take the enzymes with every meal,” she noted. “They do the nebulizer and the vest just like any other CF kid would do, sometimes two to three times a day. But they may be able to discontinue some of the therapies on the new drug.

“Sarah got engaged last month and we’re planning a wedding. The guy is wonderful. He’s always been there for her.

“I always thought 30 was a good age. I became a mother at 30. I had Sarah, then I worried about her lost opportunities. Here we are, she’s turning 30, and she’s done everything she wanted to do. She has her dream job, living her life as any other normal kid. She pushes herself, as does Jeffrey, to live life to its fullest.”

Lisa reflected on the long journey the family has endured. “I suppose at this time of the year, with Jeffrey being born on the first day of Chanukah 27 years ago, that we celebrate both Sarah and Jeffrey’s overwhelming chance of good health, happiness, and a long life because of the new medical strides being accomplished for cystic fibrosis. Ten years ago, we thought we were close…now we are in the moment where we all see a difference in their daily lives with CF and a more positive outlook for the future.”

The Cystic Fibrosis Foundation provides extensive information on CF at www.cff.org. There is information on Trikafta at www.trikafta.com.

Dr. Miryam Z. Wahrman of Teaneck is a professor of biology at William Paterson University, where she does research on microbiology and bioethics.

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