Cystic Fibrosis: Research

Progress in cystic fibrosis research has led to many new therapies that can extend and enhance the lives of those with CF. Physicians and scientists around the world are involved in a wide range of research to increase understanding of the disease.

Researchers hope to discover and develop new and effective treatments that will improve the quality of life and lengthen life for people with cystic fibrosis.

Research by dedicated scientists and clinicians includes basic science, clinical and real-world research:

• Basic science or bench research happens in laboratories. It looks at CF from molecular, cellular and tissue levels.

• Clinical research takes findings from basic science and translates them into potential treatments. These could include new ways to diagnose cystic fibrosis, new procedures and drugs to treat the disease and other new tools to help physicians and patients.

• Real-world research looks at situations of patients in the real world to examine human behavior and how it relates to treatment approaches. Learn more at the Cystic Fibrosis Foundation website.

Research Milestones

Here is an abbreviated list of research achievements for cystic fibrosis from the Cystic Fibrosis Foundation:

1938 - Dorothy Andersen, M.D., writes the first comprehensive medical report on CF.

1953 - During a heat wave in New York City, Paul di Sant'Agnese, M.D., and others connect the extra loss of salt by people with cystic fibrosis to the disease's underlying cellular problem.

1989 - A team of Foundation-supported scientists discovers the defective CF gene and its protein product (CFTR), opening the door to understanding the disease at its most basic level.

1990 - Cystic fibrosis researchers achieve "proof of concept" that gene therapy (in the laboratory) is possible.

1993 - The U.S. Food and Drug Administration (FDA) approves dornase alfa (Pulmozyme®), which is proven to thin the thick mucus in the lungs and is the first drug developed specifically for CF.

1997 - The FDA approves inhaled tobramycin (TOBI®), the first aerosolized antibiotic designed for cystic fibrosis, which is proven to reduce hospital stays and improve lung function.

2000 - Scientists map the entire genetic structure of the most common cause of CF lung infections, the bacteria Pseudomonas aeruginosa.

2002 - A clinical study shows the antibiotic azithromycin improves cystic fibrosis lung health.

2003 - Scientists at Structural GenomiX Inc. determine the three-dimensional structure of a portion of the CFTR protein, opening the door to more drug discovery opportunities.

2004 - Studies in Australia and at the University of North Carolina show that inhaled hypertonic saline helps clear CF mucus and improve lung health. It becomes a therapeutic option.

2006 - Ivacaftor (formerly VX-770), an oral drug in development that targets the faulty CFTR protein, enters clinical trials. Ivacaftor is designed to open chloride channels that do not function correctly in people with the disease.

2008 - Phase 2 studies of ivacaftor in people with the G551D mutation of cystic fibrosis show unprecedented improvements in key signs of the disease. The studies achieve "proof of concept" that it is possible to treat the root cause of CF.

2010 - The FDA approves a new antibiotic, aztreonam for inhalation solution (Cayston®), to treat cystic fibrosis lung infections. The drug offers an alternative for people with CF who battle recurrent infections and develop resistance to existing antibiotics.

2012 - The FDA approves ivacaftor (Kalydeco®) for people with the G551D mutation of CF ages 6 and older. The drug is the first to address the underlying cause of cystic fibrosis and opens exciting new doors to research and development that may lead to a cure for all people living with the disease.

2014 - The FDA approves ivacaftor as a single therapy to treat people ages 6 and older with one of nine other rare CF mutations in addition to G551D, and later extends approval to children ages 2-5 with any of these 10 mutations — representing about 8 percent of the U.S. cystic fibrosis population.

2015 -  The FDA approves the lumacaftor/ivacaftor combination drug (Orkambi®) for people with CF ages 12 and older who have two copies of the most common cystic fibrosis mutation, F508del — representing about a third of those with CF in the United States.

2016 -  The FDA approves lumacaftor/ivacaftor (Orkambi®) for children with cystic fibrosis ages 6-11 who have two copies of the F508del mutation. The decision means that about 2,400 additional children in the U.S. are eligible to receive the drug, bringing the total number of those eligible for the treatment in the U.S. to nearly 11,000.

2017 - Two Phase 3 clinical trials of tezacaftor (VX-661) in combination with ivacaftor (Kalydeco®) demonstrate positive results not only for people with two copies of the F508del mutation, but also for those who have one F508del mutation and a second mutation that results in residual function. The FDA expands the use of ivacaftor (Kalydeco®) to people ages 2 and older who have at least one of 23 residual function mutations in the CFTR gene. The FDA's consideration of laboratory evidence coupled with clinical data to address the needs of people with CF who have less common mutations is an important step forward for the cystic fibrosis community.

2018 - The FDA approves tezacaftor/ivacaftor (Symdeko®) for individuals with two copies of the most common cystic fibrosis mutation, F508del, as well as for individuals who have a single copy of one of 26 specified mutations, regardless of their other mutation. This approval paves the way for new, more effective triple-combination therapies (treatments consisting of three different modulators, including tezacaftor), which are being tested in clinical trials. The FDA approves the use of lumacaftor/ivacaftor (Orkambi®) for children with CF ages 2-5 who have two copies of the F508del mutation. The decision means that about 1,300 additional children in the U.S. are eligible to receive the drug, bringing the total number of those in the U.S. who could benefit from the treatment to approximately 12,300.

The FDA approved the use of ivacaftor (Kalydeco®) for children with cystic fibrosis ages 1-2 who have at least one mutation that is responsive to ivacaftor. The CF Foundation maintains a robust pipeline of potential therapies that target the disease from every angle. The more drugs in the pipeline, the greater the odds of producing successful therapies and a cure for all people with CF.

Source: https://www.cff.org/Research/About-Our-Research/Research-Milestones/

Learn more about cystic fibrosis research at National Jewish Health.