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The U.S. Food and Drug Administration ( FDA ) has approved Symdeko ( Tezacaftor / Ivacaftor and Ivacaftor ) for treating the underlying cause of cystic fibrosis in people ages 12 and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene or who have at least one mutation that is responsive to Tezacaftor / Ivacaftor.

In November 2017, the New England Journal of Medicine ( NEJM ) published the results of two phase 3 studies of Symdeko.
These studies, named EVOLVE and EXPAND, enrolled approximately 750 people with cystic fibrosis ages 12 and older with two copies of the F508del mutation or with one F508del mutation and one mutation that results in residual CFTR function.
Across both studies, patients treated with Symdeko experienced statistically significant and clinically meaningful improvements in lung function and other measures of disease, with a favorable safety profile.
The most common adverse events, regardless of treatment group, included infective pulmonary exacerbation and cough.

The first data from the ongoing EXTEND rollover study, also presented in November, show that the lung function improvements and the safety and tolerability profiles seen in EVOLVE and EXPAND were sustained for up to 48 total weeks of Symdeko treatment.

Some mutations result in CFTR protein that is not processed or folded normally within the cell, and that generally does not reach the cell surface.
Symdeko is a combination of Tezacaftor and Ivacaftor.
Tezacaftor is designed to address the trafficking and processing defect of the CFTR protein to enable it to reach the cell surface where Ivacaftor can increase the amount of time the protein stays open.

Cystic fibrosis is a rare, life-shortening genetic disease affecting approximately 75,000 people in North America, Europe and Australia.
Cystic fibrosis is caused by a defective or missing cystic fibrosis transmembrane conductance regulator ( CFTR ) protein resulting from mutations in the CFTR gene.
Children must inherit two defective CFTR genes ( one from each parent ) to have cystic fibrosis.
There are approximately 2,000 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic test, or genotyping test, lead to cystic fibrosis by creating non-working or too few CFTR proteins at the cell surface.
The defective function or absence of CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs.
In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death.
The median age of death is in the mid-to-late 20s. ( Xagena )

Source: Vertex, 2017

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