How Does TRIKAFTA^® Work?

VOICE-OVER:

Understanding how TRIKAFTA^® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) works

The illustrations in this video are artistic representations. They are not meant to exactly show the organ, function, or process being presented. In this video, we are going to uncover how TRIKAFTA targets the underlying cause of cystic fibrosis, or CF, in patients age 2 years and older who have at least one copy of the F508del mutation in the cystic fibrosis transmembrane conductance regulator, or CFTR, gene or another mutation that is responsive to treatment with TRIKAFTA.

You’ll see how the 3 components of TRIKAFTA work together to help responsive CFTR proteins function better, and how that can help maintain a balance of salt and water in certain organs such as the lungs. But before we dive in, let’s review who TRIKAFTA is for and some Important Safety Information.

TRIKAFTA is a prescription medicine used for the treatment of cystic fibrosis, or CF, in patients aged 2 years and older who have at least one copy of the F508del mutation in the cystic fibrosis transmembrane conductance regulator, or CFTR, gene or another mutation that is responsive to treatment with TRIKAFTA.

Talk to your doctor to learn if you have an indicated CF gene mutation.

It is not known if TRIKAFTA is safe and effective in children under 2 years of age.

Important Safety Information

Before taking TRIKAFTA, tell your doctor about all of your medical conditions, including if you have kidney problems, have or have had liver problems, are pregnant or plan to become pregnant. It is not known if TRIKAFTA will harm your unborn baby. You and your doctor should decide if you will take TRIKAFTA while you are pregnant. Are breastfeeding or planning to breastfeed. It is not known if TRIKAFTA passes into your breast milk. You and your doctor should decide if you will take TRIKAFTA while you are breastfeeding.

Please see additional Important Safety Information later in this video and at TRIKAFTA.com.

Now let’s take a closer look at how TRIKAFTA works to target the underlying cause of CF in patients with at least one F508del mutation or at least one other mutation that is responsive to TRIKAFTA. At the cell surface, cystic fibrosis transmembrane conductance regulator proteins, or CFTR proteins, play an important role in moving chloride ions into and out of cells. This movement creates a balance of salt and water.

In people with CF, chloride ions don’t move like they should because of CFTR protein defects. These defects are caused by mutations in the CF gene. CF gene mutations cause one or both of the following defects: the first defect prevents the proteins from reaching the cell surface. If the proteins do reach the cell surface, the second defect prevents them from opening correctly.

This disrupts the balance of salt and water. Without enough salt and water, thick, sticky mucus builds up on the cell surface. In the lungs, bacteria get caught in the mucus, which can lead to infection and inflammation. Now let’s turn our attention to TRIKAFTA. TRIKAFTA is a triple combination therapy that adds elexacaftor to tezacaftor and ivacaftor. Together, these 3 components target certain CFTR protein defects caused by the F508del mutation or another mutation responsive to TRIKAFTA.

By binding to different places on CFTR proteins, elexacaftor and tezacaftor get more proteins to the surface. When the proteins do reach the cell surface, ivacaftor helps them stay open longer. With all three components working together, the responsive CFTR proteins can do a better job of moving chloride ions into and out of the cells. This can help maintain a balance of salt and water in certain organs, such as the lungs, which helps keep mucus thin and free-flowing.

With this triple combination therapy, you can target the underlying cause of CF in people 2 years and older with at least one copy of the F508del mutation or another mutation that is responsive to TRIKAFTA. Please stay tuned for some additional Important Safety Information.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

TRIKAFTA may affect the way other medicines work, and other medicines may affect how TRIKAFTA works. The dose of TRIKAFTA may need to be adjusted when taken with certain medicines. Ask your doctor or pharmacist for a list of these medicines if you are not sure.

Especially tell your doctor if you take: antibiotics such as rifampin or rifabutin; seizure medicines such as phenobarbital, carbamazepine, or phenytoin; St. John’s wort; antifungal medicines including ketoconazole, itraconazole, posaconazole, voriconazole, or fluconazole; antibiotics including telithromycin, clarithromycin, or erythromycin. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

Avoid food or drink that contains grapefruit while you are taking TRIKAFTA.

TRIKAFTA can cause serious side effects, including liver damage and worsening of liver function in people with severe liver disease that can be serious and may require transplantation. Liver damage has also happened in people without liver disease.

High liver enzymes in the blood, which is a common side effect in people treated with TRIKAFTA. These can be serious and may be a sign of liver injury. Your doctor will do blood tests to check your liver before you start TRIKAFTA, every 3 months during your first year of taking TRIKAFTA, then every year while you are taking TRIKAFTA. Your doctor may do blood tests to check the liver more often if you have had high liver enzymes in your blood in the past.

Call your doctor right away if you have any of the following symptoms of liver problems: pain or discomfort in the upper right stomach, or abdominal, area; yellowing of your skin or the white part of your eyes; loss of appetite; nausea or vomiting; dark, amber-colored urine.

Abnormality of the eye lens, also known as cataract, has happened in some children and adolescents treated with TRIKAFTA. If you are a child or adolescent, your doctor should perform eye examinations before and during treatment with TRIKAFTA to look for cataracts.

The most common side effects of TRIKAFTA include headache; upper respiratory tract infection, or common cold, including stuffy and runny nose; stomach, or abdominal, pain; diarrhea; rash; increase in liver enzymes; increase in a certain blood enzyme called creatine phosphokinase; flu, or influenza; inflamed sinuses; or increase in blood bilirubin.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of TRIKAFTA. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You are encouraged to report side effects to FDA at 1-800-FDA-1088.

Please see the links for Important Safety Information and full Prescribing Information, including Patient Information, below.

This video is brought to you by Vertex Pharmaceuticals Incorporated.