FDA Approves Trikafta, New “Triple Combo” Therapy for CF
This week, the US Food and Drug Administration approved the first “triple therapy” treatment option for a large proportion of people with CF. The medication, Trikafta™, combines three different drugs, known as the "triple combo." These drugs are elexacaftor, ivacaftor, and tezacaftor. Trikafta™ was approved for use in people with CF who at least 12 years old, and who have a specific genetic mutation. This medication is designed for people with CF who have the F508del mutation in their CFTR (cystic fibrosis transmembrane conductance regulator) gene, an important gene that is affected in the development of CF. About 90% of all peoples with CF are thought to have at least one F508del mutation, meaning this triple therapy may be a groundbreaking development for the CF community.1,2
What is the role of CFTR modulators in cystic fibrosis?
The way Trikafta™ impacts the body is complex, but overall, it helps proteins that have been impacted by the CFTR gene mutation work better. Without treatment, these proteins can contribute to the development and worsening of CF symptoms. Drugs like Trikafta™ are called CFTR modulators. Trikafta™ increases the number CFTR proteins on the outside of specific cells and helps these proteins work better in an effort to decrease CF-related symptoms. In people with CF, there are different mutations within CFTR proteins that impact how CFTR modulators can be harnessed in order to treat the condition. However, Trikafta™ has been developed specifically for people with CF who have the most common gene mutation, making this a drug that may transform CF treatment.1,2
What does the research say about Trikafta?
Trikafta’s™ approval came after the FDA reviewed results from two clinical trials on the new triple therapy. The first trial included over 400 individuals ages 12 and older who had at least one F508del mutation and lasted for 24 weeks. The second trial had over 100 individuals with the same qualifications, but lasted four weeks. The participants in the first trial had a second, different mutation within their genes that also impacted the CFTR protein and made them non-responsive to other common treatment options currently available (including the combination of tezacaftor and ivacaftor alone, without the added elexacaftor). Individuals in the second trial had two identical F508del mutations.1,2
Both of these studies looked at an important measure of CF progression--the percent of predicted forced expiratory volume of air that a person can exhale in one second (ppFEV1). Participants taking Trikafta™ in both studies had a positive ppFEV1 response to treatment, with individuals in the first study having a 14% improvement in ppFEV1 compared to those taking a placebo, and individuals in the second study having a 10% improvement compared to those taking tezacaftor/ivacaftor alone. Additionally, those in the first trial also showed improvements in body mass index (BMI), episodes of worsening respiratory symptoms (pulmonary exacerbations), and sweat chloride when compared to those taking placebo. All of these results suggest that Trikafta™ may improve CF-related symptoms and lung function for those with at least one F508del mutation.1,2
Side effects of Trikafta™ on cystic fibrosis patients
The most common side effects of Trikafta™ reported during these trials were upper respiratory tract infections, diarrhea, abdominal pain, rash, headache, congestion or mucus in the nose, sinus infections, and influenza (flu). Side effects like rash or flu may become severe over time and be considered serious side effects.1,2
Some people taking Trikafta™ may also experience changes in specific enzymes (proteins) in the blood, such as liver enzymes, and may have an increase in bilirubin counts. Bilirubin is related to liver, red blood cells, and gallbladder functioning. Some people may not be able to take Trikafta™ because of these changes and will need more frequent monitoring. Trikafta™ also comes with a warning against taking the triple therapy along with some other medications, as well as a warning for the risk of developing cataracts. Your healthcare provider will help you explore these options and determine whether it is safe for you to take Trikafta™.1,2
Moving forward with Trikafta™ for cystic fibrosis
People with CF can find out more about what genetic mutations they may have by undergoing genetic testing. Your healthcare provider can help guide you through this process. Trikafta™ was quickly approved for use through several programs, including FDA’s Priority Review, Fast Track, and Breakthrough Therapy Designation processes due to its potential positive impact on the CF community. Currently, Trikafta™ is being studied for use in individuals younger than 12 years old, and results from these trials should be released within the next year.1,2
Have you (or a loved one) been experiencing any negative side effects from Trikafta?