What to Know About CFTR Modulator Cystic Fibrosis Medications
Key takeaways:
Cystic fibrosis occurs when a genetic alteration causes changes to the cystic fibrosis transmembrane conductance regulator (CFTR protein). CFTR modulators help the CFTR protein work better.
Kalydeco was the first CFTR modulator available, followed by Orkambi, Symdeco, and Trikafta. Each medication only works for specific genetic changes, so they aren’t a treatment option for everyone living with cystic fibrosis. Your pulmonologist will use genetic testing to see if they’re an option for you.
If you‘re not a good candidate for CFTR modulators, there are still effective treatment options available. And research is underway to find other effective cystic fibrosis treatments.
Table of contents
For decades, the only treatment options for cystic fibrosis were medications aimed at preventing lung infections and managing the symptoms of the condition. But in 2012, that changed with a new class of medication called cystic fibrosis transmembrane conductance regulator (CFTR) modulators. CFTR modulators target the underlying cause of cystic fibrosis, not just the symptoms. But what are these cystic fibrosis medications, and how do they work?
How do CFTR modulators work to treat cystic fibrosis?
CFTR modulators are oral medications that address the root cause of cystic fibrosis. Cystic fibrosis is caused by genetic changes that affect the CFTR protein. These changes prevent the protein from working properly, which leads to thick, sticky mucus that can build up in your lungs and other organs. CFTR modulators help the CFTR protein work better.
There are currently two main types of FDA-approved CFTR modulators:
Potentiators help the CFTR protein move water and other nutrients into mucus to keep it thin and fluid.
Correctors help the CFTR protein hold the right shape to work properly.
There are over 2,000 different genetic changes that can cause cystic fibrosis. And each one causes a different type of problem with the CFTR protein. But the currently approved CFTR modulators only work for certain genetic changes. So they aren’t an option for everyone. You’ll need genetic testing to figure out what type of genetic change you have. This will allow your pulmonologist (lung specialist) to select the best treatment options for you.
Keep in mind that even if you’re not eligible for CFTR modulators now, research is underway to find new treatments. Talk to your healthcare team about whether these clinical trials may be an option for you.
Let’s take a closer look at the four CFTR modulators available in the U.S.
1. Kalydeco
Kalydeco (ivacaftor) is a potentiator that helps the CFTR protein move salt and water between cells to keep mucus thin. It was the very first CFTR modulator available in the U.S. and treats 97 different genetic changes that cause cystic fibrosis.
Who can use it: Kayldeco is approved for adults, children, and infants that are at least 1 month old.
How you take it: Kalydeco comes in tablets as well as packets of oral granules that you can mix into cold or room-temperature food or drinks. For adults and children ages 6 years and older, the dosage is 150 mg (one tablet) twice a day. For younger children and infants, the dose is based on body weight. You should take both forms of Kalydeco with fatty foods such as eggs, peanut butter, or whole-milk dairy products.
Side effects: CFTR modulators all have similar side effects, including headache, upset stomach, and nasal congestion. Upper respiratory infections, such as the common cold, are also frequently reported. More serious side effects include trouble breathing, liver problems, and mood changes. Let your prescriber know if you experience these side effects. They may be able to manage them by lowering your Kalydeco dosage.
2. Orkambi
Orkambi (lumacaftor / ivacaftor) contains two active ingredients. Ivacaftor is the potentiator that’s also the active ingredient in Kalydeco. But Orkambi also contains lumacaftor, a corrector that helps the CFTR protein hold its shape. It’s only effective for a genetic change known as F508del. And the change must be present in both genes (homozygous) in order for Orkambi to work.
Who can use it: Orkambi is approved for adults and children ages 1 year and older.
How you take it: Orkambi comes in tablets and packets of oral granules. Oral granule dosing is based on body weight for children ages 5 and under. Adults and children ages 6 and older can take the tablets. But Orkambi dosing requires two tablets twice a day, so there are more tablets to swallow than with Kalydeco. You should also take Orkambi with fatty foods.
Side effects: Orkambi is more likely to cause trouble breathing or shortness of breath than the other CFTR modulators. So it may not be the best choice for those with severe lung problems. Your pulmonologist may recommend an inhaled medication along with Orkambi to help open your lungs and lessen this side effect.
3. Symdeko
Symdeko (tezacaftor / ivacaftor) contains two active ingredients: tezacaftor (a corrector) and ivacaftor (a potentiator). It works in a similar way to Orkambi, but Symdeko treats more genetic changes. It works for those with two copies of the F508del variation. And it also works for those with one copy of the F508del variation and a second genetic change that’s covered by ivacaftor.
Who can use it: Symdeko is approved for adults and children ages 6 years and older.
How you take it: Symdeko is available as an oral tablet taken every 12 hours. The morning tablet contains both tezacaftor and ivacaftor, but the evening tablet only contains ivacaftor. So it’s important to be sure you’re taking the right tablet at the right time. As with the other CFTR modulators, you should take Symdeko with a fatty meal or snack.
Side effects: Symdeko seems to have a lower risk of side effects and drug interactions than Orkambi. So it may be a preferred choice for people with severe lung problems or those taking medications that interact with Orkambi.
4. Trikafta
Trikafta (elexacaftor / tezacaftor / ivacaftor) is a CFTR modulator that adds a second corrector (elexacaftor) to the ingredients found in Symdeko. It’s the most effective CFTR modulator currently available. Trikafta is approved for anyone with at least one F508del variation or any other genetic change that’s sensitive to the medication. This includes about 90% of people living with cystic fibrosis.
Who can use it: Trikafta is approved for adults and children ages 2 years and older.
How you take it: Trikafta comes in oral tablets as well as packets of oral granules that you’ll take twice a day. Similar to Symdeko, the morning dose contains all three ingredients and the evening dose only contains ivacaftor. But for Trikafta, the morning dose requires two tablets instead of one for adults and children over the age of 6. The oral granule dosage for children under 6 years old is based on body weight. You should take Trikafta with a fatty meal or snack.
Side effects: Trikafta has similar side effects to other CFTR modulators, including nausea and diarrhea. Starting with a lower dosage of Trikafta may lessen the chance of some side effects. Your pulmonologist will determine the best dosage for you based on your medical history.
What are other common medications used for cystic fibrosis?
CFTR modulators aren’t typically used on their own. You’ll likely need other medications to manage your symptoms. If CFTR modulators aren’t an option for you, these medications will serve as your main forms of treatment.
The other types of medications used to treat cystic fibrosis include:
Antibiotics: Oral, intravenous (IV), and inhaled antibiotics treat and prevent infections that happen when thick mucus builds up in the lungs. Examples include tobramycin (Tobi) and sulfamethoxazole / trimethoprim (Bactrim).
Bronchodilators: These inhaled medications, such as albuterol (ProAir, Proventil, Ventolin), help widen the airways and allow easier breathing.
Mucus thinners: These inhaled medications help thin the sticky mucus in your lungs. Examples include dornase alpha (Pulmozyme) and sodium chloride.
Pancreatic enzymes: Cystic fibrosis can cause a build-up of mucus in the pancreas, which can block the release of enzymes that help you digest your food. But you can take these enzymes in capsule forms, such as pancrelipase (Creon), to help you absorb the nutrients you need.
How to save on CFTR modulators
There are ways to save on CFTR modulators, which are only available as brand-name medications. GoodRx can help you navigate between patient assistance programs and copay savings cards to save money on your prescription.
Save with a copay savings card. If you have commercial insurance, you may be eligible to pay as little as $0 using a savings card from the manufacturer. Kalydeco, Orkambi, Symdeco, and Trikafta are all included in this savings program.
Save with patient assistance programs. If you’re uninsured or underinsured, you may be eligible for the manufacturer’s patient assistance program, which offers these four CFTR modulators free of cost.
Good to know: CFTR modulators are limited distribution drugs, which means not every pharmacy carries them. You’ll likely need to have your prescription filled at a specialty pharmacy, and it may take longer than usual to process and receive the medication. The good news is that specialty pharmacies will often go the extra mile to help you get insurance approval and/or take advantage of discounts and programs to help you afford your medication.
The bottom line
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are a game-changing treatment option for many people living with cystic fibrosis. These medications work to address the root cause of cystic fibrosis: genetic variations that change the way the CFTR protein works.
Each CFTR modulator helps the CFTR protein work better in a different way. And they only work for certain genetic changes, so they’re not a treatment option for everyone. Your pulmonologist will use genetic tests to figure out if these medications are an option for you.
If you are not a good candidate for CFTR modulators, there are still effective treatment options available. And new research is underway to find more CFTR modulators and other effective treatments.
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References
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