On October 21, 2019 the United States Food and Drug Administration approved a breakthrough treatment for patients with cystic fibrosis. This drug is a triple-combination modulator elexacaftor/tezacaftor/ivacaftor (Trikafta™) for people with cystic fibrosis ages 12 and older who have at least one copy of the F508del mutation.  Until the approval of this medication, most patients with only one copy of the F508del mutation did not have an approved treatment for the underlying cause of cystic fibrosis.  Additionally, the patients with two copies of the mutation saw an increase in lung function of an average of 10% as compared with the current available treatments.

Cystic fibrosis, considered a rare disease, is the most common cause of severe chronic lung disease in young adults and pediatric patients in the United States.  It is the most common hereditary disorder leading to fatality among Caucasians. It is autosomal-recessive, with 1 in 25 Caucasians being carriers and 1 in 3,000 being affected. Cystic fibrosis does occur in other ethnic groups, but much less commonly.  For example, according to the National Institutes of Health cystic fibrosis affects about 1 in 17,000 African Americans and 1 in 31,000 Asian Americans.

The pathophysiologic defect causing cystic fibrosis is due to an abnormality of the sodium-chloride channel (the cystic fibrosis transmembrane conductance regulator [CFTR] protein). This leads to impaired or completely ineffective chloride and water transport across the cell membrane. This defect leads to abnormally thick mucus production as the mucus is not adequately hydrated. Patients often develop bronchiectasis, recurrent pulmonary infections, and infections with pan-resistant organisms. The primary cause of mortality is respiratory failure. Patients often ultimately require lung transplantation. Patients have abnormally thick secretions is all areas of the body, including the pancreas. Patients develop pancreatic insufficiency and autodigestion, requiring pancreatic enzyme replacement and often develop cystic fibrosis-related diabetes.

Patients vary greatly in their presentation and associated symptoms as there are over 1,000 different mutations in the gene that encodes for the CFTR protein.  About 60% of patients have a mutation called D F508 (F508del), which has been the target of many breakthrough therapies.  Many breakthroughs for cystic fibrosis have been achieved in the recent years, including this novel medication.  About one-third of the patients living with cystic fibrosis are now adults.  The median age of survival is now over 39 years, which has increased dramatically over the past two decades.  More work needs to be done to further increase the quality of life and survival for this patient population.

Read more:

Current Medical Diagnosis and Treatment 2020: Cystic Fibrosis

Cystic Fibrosis Foundation

Harrison’s Principles of Internal Medicine, 20e: Chapter 285: Cystic Fibrosis

National Institute of Health