Cystic Fibrosis
Cystic fibrosis (CF) is a rare disease caused by the lack (or malfunctioning) of the cystic fibrosis transmembrane conductance regulator (CTFR) protein. This occurs when children inherit a mutated CFTR gene from both parents. It causes the flow of water and salt between cells to be impaired. This results in a buildup of mucus in the lungs, ultimately producing chronic lung infections and irreversible damage. Most patients do not live past their late 20s.
However, recent results from a Phase 3 trial in Europe have shown promise for a new potential therapy for CF.
The Trial
This Phase 3 trial was conducted by Vertex Pharmaceuticals in Australia and Europe. It examined the effect of tezacaftor and ivacaftor in CF in patients age 6 to 11. All participants had either one copy of the F508del mutation plus one residual function mutation or two copies of F508del.
The combination of tezacaftor and ivacaftor is called SYMDEKO. These drugs work together to combat the mutations in CFTR. The Phase 3 trial examining this treatment included 67 participants total. 54 received SYMDEKO, 10 received placebo, and 3 received only ivacaftor. The trial lasted 8 weeks.
The trial’s primary endpoint was change in lung clearance index (LCI) which measures ventilation of the lungs. A higher LCI means poorer lung function whereas a lower LCI indicates better function. In order to even join the study, patients had to have a LCI of 7.5. By the end of the study, the children given SYMDEKO achieved a LCI of -0.51. Therefore, this primary endpoint was met.
The safety data from this study was consistent with previous trials investigating these drugs and the treatments were generally well tolerated. There were no serious adverse events (AEs) reported in this study and no patient had to stop treatment due to complications. The most common AEs for those given SYMDEKO were headache and cough.
Looking Forward
The reason this study was conducted was ultimately to support Vertex’s application of the combined treatment to the European Medicines Agency. They plan to submit this application in the second half of this year.
The company has already submitted a Supplemental New Drug Application to the FDA for this combination treatment based on a study conducted in the United States/Canada.
You can read more about this combination treatment and Vertex’s work in cystic fibrosis here.
