Alyftrek (vanzacaftor/tezacaftor/deutivacaftor) is a combination medicine approved by the FDA in 2024. Alyftrek is approved to treat people ages 6 and older who have the genetic condition called cystic fibrosis. Cystic fibrosis happens because of a change in a gene on chromosome 7. This gene is responsible for making a protein called the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which helps control the movement of salt and water in the body. Cystic fibrosis changes the way chloride (salt) moves through the cells of your body. This causes the mucus (which should be thin and slippery) in various organs to become thick and sticky, which can lead to infections, inflammation, problems with your organs, and electrolyte imbalances. Symptoms of cystic fibrosis can appear at any age from infancy to adulthood.
How Does Alyftrek Work?
Alyftrek is a type of medicine called a CFTR modulator. Alyftrek is designed to help make the broken CFTR protein in people with cystic fibrosis work better. Since different genetic mutations can cause different types of problems with the protein, the medicines available today only work for people with certain mutations. Alyftrek is approved for people who have at least one F508del mutation or another responsive mutation in the CFTR gene. Alyftrek contains three active ingredients (vanzacaftor, tezacaftor, and deutivacaftor) that work together to help the CFTR protein work better. Vanzacaftor and tezacaftor help the CFTR protein fold correctly and move to the cell surface, while deutivacaftor increases CFTR activity to lower the buildup of mucus. By helping CFTR work better, Alyftrek helps thin mucus in the lungs and other organs, making it easier to clear and reducing complications of cystic fibrosis.
How Do I Take Alyftrek for Cystic Fibrosis?
Your health care provider will decide the correct dose of Alyftrek based on your age and weight.
Alyftrek is a tablet that is taken by mouth. It should be swallowed whole with food that contains fat, such as eggs, nuts, meats, or dairy products, to help the body absorb the medicine properly.
The treatment plan usually follows these steps after receiving the recommended liver evaluations and tests:
- For people aged 6 to <12 years (<40 kg): Take three tablets (vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg) once daily with fat-containing food.
- For people aged 6 to <12 years (≥40 kg) or ≥12 years: Take two tablets (vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg) once daily with fat-containing food.
Dose adjustments may be needed in people with liver problems. Alyftrek should be taken at the same time each day to maintain steady levels of the medicine in the body.
Keep all appointments with your health care provider before and while taking Alyftrek. Your health care provider may monitor how well your liver is working.
How Was It Studied for the Treatment of Cystic Fibrosis?
The effectiveness and safety of Alyftrek for cystic fibrosis was studied in two randomized trials (Trials VX20-121-102 and VX20-121-103). These studies compared Alyftrek to another standard treatment for cystic fibrosis (elexacaftor/tezacaftor/ivacaftor). People in the studies first received elexacaftor/tezacaftor/ivacaftor for four weeks, then were assigned to continue this treatment or switch to Alyftrek for 52 weeks. Trial VX20-121-102 included 398 people with F508del-minimal function genotypes. The median (middle) age was 31 and 41% of people were female; most people in the study were White (97%), while 1% were Black or African American, and <1% were Asian. Trial VX20-121-103 included 573 people with F508del-F508del, F508del-residual function, F508del-gating, or other responsive mutations. The median age was 33.1 and 49% of people in the study were female. Most people were White (93%), 1% were Black or African American, and <1% each were Southeast Asian, other Asian, or American Indian/Alaska Native.
The study found that Alyftrek was similar to elexacaftor/tezacaftor/ivacaftor in improving lung function (measured by forced expiratory volume in 1 second [FEV1 %]), with similar results seen in both studies. Additionally, Alyftrek led to greater reductions in sweat chloride, a key measure of CFTR function, in both studies. The results of these studies suggest that Alyftrek is a promising alternative to elexacaftor/tezacaftor/ivacaftor, offering similar lung function benefits and helping CFTR to work better.
The safety profile of Alyftrek was similar to that of elexacaftor/tezacaftor/ivacaftor. The most common side effects included worsening lung infections (28%), cough (23%), COVID-19 (22%), and the common cold (nasopharyngitis; 21%). Serious side effects were similar between groups, with 14% of people treated with Alyftrek and 16% of people treated with standard treatment experiencing severe reactions. High liver enzymes were slightly more common in the Alyftrek group, but overall safety findings were similar to those seen in other studies.
Your results may differ from what was seen in clinical studies.
Who Was Included in These Studies?
Overall, Alyftrek for cystic fibrosis treatment has been studied in a variety of people.
- Adults
- Adolescents
- Males and females
- Asian, Black, and White people
How Strong Is the Evidence for Alyftrek?
Based on the current clinical studies, Alyftrek is a safe and effective treatment for people with cystic fibrosis. The Cystic Fibrosis Foundation published a CFTR modulator therapy care guideline in 2018. Alyftrek is not included in these guidelines since it was approved by the FDA after these guidelines were published.
How Do I Know if Alyftrek Is Working?
Your health care provider will monitor your progress while you are taking Alyftrek to make sure the treatment is effective. One key test used to measure progress is lung function testing (like FEV₁%), which checks how well your lungs are working. If Alyftrek is working, your FEV₁% may get better or remain the same over time.
Another important measure is sweat chloride levels. Higher sweat chloride levels are a sign of cystic fibrosis, and Alyftrek may help lower these levels by helping the CFTR protein work better. Your health care provider may order sweat chloride tests to track improvements.
In addition to lab tests, you may notice fewer lung infections, better breathing, less coughing, and increased energy levels. Your health care provider will also monitor for any side effects and may adjust your treatment plan if needed. Always follow up with your health care team to discuss any changes in symptoms or concerns about your treatment.
Do not stop taking Alyftrek without talking to your health care provider first. Your symptoms may get worse again if you stop or change any of your medicines.
What Are Other Unique Considerations to Be Aware of During Treatment?
The most common side effects of Alyftrek are cough, common cold, sinus infection, headache, sore throat, flu, feeling tired, skin rash, and changes in liver enzyme levels.
If you experience a serious allergic reaction, such as difficulty breathing, swelling of the face, or severe dizziness, seek medical attention immediately.
Liver problems, such as increased liver enzyme levels, may occur. Your doctor will monitor liver function with routine blood tests. Report any signs of yellowing skin or eyes (jaundice), dark urine (pee), or unexplained tiredness to your health care provider.
Regular eye exams are also recommended since Alyftrek may cause cataracts, especially in younger people. Routine check-ups can help detect early changes in vision.
These are not all of the possible side effects. Talk with your health care provider if you are having symptoms that bother you. Depending on the severity of your side effects, your health care provider may pause, reduce the dose, or permanently discontinue treatment with Alyftrek. In the U.S., you can also report side effects to the FDA at www.fda.gov/medwatch or by calling 800-FDA-1088.
What Types of Drug Interactions Can Happen?
Your body uses special enzymes called CYP450 to break down certain medicines. When you have long-term illness, your body may produce more or less of these enzymes, which can change how some medicines work.
Some medicines and foods may affect the levels of these enzymes, which could impact how Alyftrek works in your body.
- Avoid CYP3A Inducers: Some medicines called CYP3A inducers (e.g. carbamazepine or rifampin) can lower the amount of Alyftrek in your body, making it less effective.
- Be Cautious with CYP3A inhibitors: CYP3A inhibitors (e.g. erythromycin or itraconazole) can increase the levels of Alyftrek in the body, which may raise the risk of side effects. If you are taking one of these medicines, your health care provider may adjust your Alyftrek dose.
- Avoid grapefruit products: Grapefruit and grapefruit juice can also increase the amount of Alyftrek in the body, so it is best to avoid them while on this medicine.
Alyftrek can also affect how other medicines work in your body.
- P-gp and BCRP substrates: Alyftrek may increase the levels of certain medicines that rely on P-gp (P-glycoprotein) and BCRP (breast cancer resistance protein) in the body. This could lead to stronger effects or more side effects from those medicines. Your health care provider may monitor you more closely if you are taking one of these medicines.
- CYP2C9 substrates (e.g., warfarin): Alyftrek may interfere with CYP2C9 substrates, such as warfarin, a blood thinner. If you take warfarin, your doctor may need to check your blood clotting levels more often.
Always tell your health care provider about any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using or have recently taken. This will help make sure your medicines work well together.
Are There Any Special Steps Required to Get Alyftrek?
Alyftrek is a specialty medicine. This means that you can only get it from a specialty pharmacy and it may require prior authorization from your insurance company.
Is There Any Cost Assistance Available?
There is a savings coupon available from the drugmaker that may allow you to pay as little as $0 for your prescription. Whether you are eligible depends on whether you have prescription insurance and what type of insurance you have. You can find out more at Vertex GPS™ Patient Support Program | ALYFTREK™ (vanzacaftor/tezacaftor/deutivacaftor).