SYMDEKO™ for Cystic Fibrosis: 873896

SYMDEKO™ for Cystic Fibrosis

Cystic fibrosis is a severe genetic disorder which mostly affects the lungs of the patients. It can be defined as a progressive genetic disorder that leads to the persistent infections in the lung and also limits the breathing power of the victim as well. Although the disease has not effective cure, very few choices of life saving medication is available that can slow down the progress of the disease (2). Symdeko is one such medicine which is given to the patients that are suffering from cystic fibrosis. The mechanism of action of this drug is complex, it contains a combination of ivacaftor and tezacaftor, and both of the active agents perform inter-related actions to target the clinical manifestations of cystic fibrosis. Elaborating further, the Tezacaftor targets the defective CFTR protein and moves it onto the cell the surface. Ivacaftor on the other hand helps to facilitate opening of the chloride channels on the surface of the cell to enhance the chloride transport (1).

Question 2:

            Symdeko has been a new drug that has been introduced in the clinical care for cystic fibrosis. As mentioned by the Gentzsch et al. the new drug Symdeko having the combination of ivacaftor and the corrector tezacaftor had been effective in reversing the harmful effects of the most common CFTR protein mutations. Along with that, this particular precision medication has also been approved by the FDA and has been set to be released in European market for the effectiveness of the drug (1). Hence, it can be considered that this drug had been effective till date for treating selective CFTR mutations.

Question 3:

There are a variety of different mutations caused in the CFTR coding region that can lead to the development of the cystic fibrosis in the patients (4). It has to be mentioned, not all of the mutations can be treated by the same medication. Elaborating more, it has to be mentioned that the mutations to CFTR gene that has been identified in the last few years of research have been categorized in 5 different major classes of medication. Among the 5 classes of mutation of the CFTR, the class I, II, and III have been pegged as the most severe of the mutations in the CFTR gene leading to severe pancreatic insufficiency and decreased survival. On the other hand, the class IV and V have been categorized as the mild mutations associated with pancreatic sufficiency (2).

Hence, it is to be acknowledged that the mutations each have different trajectory of alterations in the physiological functions and different to different clinical manifestations. Hence, for treatment as well, the medications that are being utilized must take into consideration the particular type of mutation, or at least the class, so that the exact alterations can be reversed and cellular functions can be reversed. In case potentiator drugs are used it facilitates the movement out of the ER. For instance, the Symdeko has two components, ivacaftor that targets the G551D mutation and tezacaftor that targets the F508del mutation, hence this medication will yield fruitful results for these mutations only (4). Therefore, it can be stated that it is crucial to use different drugs to treat different mutations of the CFTR.


  1. Wise J. MPs call for fresh talks to end deadlock over cystic fibrosis drug. BMJ: British Medical Journal (Online). 2018 Mar 21;360.
  2. Gentzsch M, Cholon DM, Quinney NL, Boyles SE, Martino ME, Ribeiro CM. The Cystic Fibrosis Airway Milieu Enhances Rescue of F508del in a Pre-Clinical Model. European Respiratory Journal. 2018 Jan 1:1801133.
  3. Sala MA, Jain M. Tezacaftor for the treatment of cystic fibrosis. Expert review of respiratory medicine. 2018 Sep 2;12(9):725-32.
  4. Van Goor F, Yu H, Burton B, Hoffman BJ. Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. Journal of Cystic Fibrosis. 2014 Jan 1;13(1):29-36.