From the Guidelines
Trikafta is a medication that contains three active ingredients—elexacaftor, tezacaftor, and ivacaftor—which work together to treat cystic fibrosis (CF) in patients with specific genetic mutations. Each component has a distinct function in addressing the underlying cause of CF.
- Elexacaftor and tezacaftor both work as CFTR correctors, meaning they help the defective CFTR protein fold correctly and reach the cell surface.
- Specifically, they bind to different sites on the CFTR protein, enhancing its processing and trafficking to the cell membrane.
- Ivacaftor functions as a CFTR potentiator, which means it increases the activity of the CFTR protein once it reaches the cell surface by keeping the chloride channel open longer, as described in the study 1. This allows for improved chloride ion transport across cell membranes. Together, these three medications significantly improve lung function in CF patients by increasing the quantity and function of CFTR proteins at the cell surface, which helps thin mucus secretions in the lungs and other organs. This combination therapy is particularly effective for patients with at least one F508del mutation, the most common CF-causing mutation, as supported by the evidence from 1. The use of ivacaftor has been shown to improve rhinologic QOL in patients with CF evaluated by SNOT-20, and has also demonstrated several other beneficial off-target effects, including a beneficial impact on chronic rhinosinusitis, as noted in the study 1. Overall, the combination of elexacaftor, tezacaftor, and ivacaftor in Trikafta provides a comprehensive approach to treating CF by addressing the underlying defect in CFTR protein function, and is supported by the evidence from 1.
From the FDA Drug Label
Elexacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of select mutant forms of CFTR (including F508del-CFTR) to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The functions of each ingredient in the brand name drug "Trikafta" are:
- Elexacaftor: facilitates the cellular processing and trafficking of select mutant forms of CFTR to increase the amount of CFTR protein delivered to the cell surface
- Tezacaftor: facilitates the cellular processing and trafficking of select mutant forms of CFTR to increase the amount of CFTR protein delivered to the cell surface
- Ivacaftor: potentiates the channel open probability (or gating) of the CFTR protein at the cell surface 2
From the Research
Functions of Elexacaftor, Tezacaftor, and Ivacaftor in Trikafta
The brand name drug "Trikafta" is a combination of three individual drugs: elexacaftor, tezacaftor, and ivacaftor. The functions of these ingredients are:
- Elexacaftor: a corrector of the CFTR protein, which helps to increase the activity of the cystic fibrosis transmembrane conductance regulator (CFTR) protein 3, 4, 5
- Tezacaftor: a corrector of the CFTR protein, which works together with elexacaftor to increase the activity of the CFTR protein 3, 4, 5
- Ivacaftor: a potentiator of the CFTR protein, which helps to increase the activity of the CFTR protein by enhancing the opening of the CFTR channel 3, 4, 5
Mechanism of Action
The combination of elexacaftor, tezacaftor, and ivacaftor in Trikafta works by increasing the activity of the CFTR protein, which helps to reduce the mortality and morbidity rates in CF patients 3. The trio also reduces the expression of P2X7R, a receptor that promotes inflammasome activation, and decreases the levels of circulating proinflammatory markers 6.
Clinical Benefits
The clinical benefits of Trikafta include: