The U.S. Food and Drug Administration (FDA) today approved a new drug that treats the underlying cause of cystic fibrosis, expanding the number of people with CF who could benefit from cystic fibrosis transmembrane conductance regulator (CFTR) modulators. This approval paves the way for new, more effective triple combination therapies (treatments consisting of three different modulators, including tezacaftor) scheduled to begin late stage clinical trials in the next several months.

Tezacaftor/ivacaftor (Symdeko™) is approved for people with CF ages 12 and older who have two copies of the most common CF mutation, F508del, providing another option for people in this population, particularly individuals who could not tolerate a similar drug, lumacaftor/ivacaftor (Orkambi^®). Around 46 percent of the more than 30,000 people with CF in the U.S. have two copies of F508del.

The drug also was approved for people with CF ages 12 and older who have a copy of one of 26 specified mutations (listed below) of the key protein involved in cystic fibrosis, CFTR. These mutations were selected based on a combination of clinical and laboratory data.

“Today's approval is exciting news for the cystic fibrosis community and a big step forward in our ongoing efforts to find new and better treatments to address the underlying cause of the disease,” said Preston W. Campbell, III, M.D., president and CEO of the CF Foundation. “We are optimistic that next-generation CFTR modulators that build on this advance could bring transformative treatments to nearly 90 percent of people with CF, and we remain committed to finding effective new treatments for every individual living with the disease.”

Understanding Tezacaftor/Ivacaftor

Tezacaftor/ivacaftor is a drug that improves the function of the CFTR protein. Cystic fibrosis occurs when the CFTR protein is either not made correctly, or not made at all.

In late stage clinical trials, people with two copies of the F508del mutation who had taken the tezacaftor/ivacaftor combination improved their lung function by 4 percentage points compared to those taking a placebo. Participants in the studies also experienced improvements in other key measures of the disease, including a 35 percent reduction in exacerbations (a sudden worsening of symptoms that requires treatment) and an increase in the measurement used to assess quality of life.

People with at least one copy of the 26 specified mutations who took tezacaftor/ivacaftor in late-stage clinical trials improved lung function by 6.8 percentage points compared to those taking a placebo.

Critically, people who took tezacaftor/ivacaftor were less likely to experience tightness in the chest and potential drug interactions, which was observed in a subset of patients on lumacaftor/ivacaftor. (Lumacaftor/ivacaftor is approved for use in people with two copies of the F508del mutations in people with cystic fibrosis ages 6 and older.)

“Symdeko is an important addition to the growing CF treatment arsenal and a much-needed option for individuals with the most common CF mutation,” Michael Boyle, M.D., senior vice president for therapeutics development at the CF Foundation. “We are grateful to the hundreds of people with CF who took part in the clinical trials that made this advance possible and to those in the ongoing trials that hold great promise for our community.”

Looking Ahead to Triple Combinations

Early studies strongly suggest that triple combination therapies are potentially more effective and could treat significantly more people than previously approved modulators. Additionally, the trials that tested tezacaftor, ivacaftor, and a third modulator therapy showed positive results in individuals with only one F508del mutation, regardless of their second mutation. Two of these potential triple combination therapies will begin clinical trials by mid-2018.

Tezacaftor/ivacaftor was developed by Vertex Pharmaceuticals Inc. with significant clinical, scientific, and funding support from the Cystic Fibrosis Foundation.

People with CF who are eligible for tezacaftor/ivacaftor include people who have two copies of the F508del mutation and people who have a single copy of one of the following mutations in this table:

For additional information, please see the Vertex release.