FDA Approves New Breakthrough Therapy for Cystic Fibrosis

October 22, 2019

The US Food and Drug Administration (FDA) has approved the first triple combination therapy to treat patients aged 12 years and older with cystic fibrosis who have at least 1 F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is estimated to represent 90% of the cystic fibrosis population.

“In the past few years, we have seen remarkable breakthroughs in therapies to treat cystic fibrosis and improve patients’ quality of life, yet many subgroups of patients with cystic fibrosis did not have approved treatment options,” said Ned Sharpless, MD, FDA, Rockville, Maryland. “That’s why we used all available programs, including Priority Review, Fast Track, Breakthrough Therapy, and orphan drug designation, to help advance today’s approval in the most efficient manner possible, while also adhering to our high standards. The FDA remains committed to advancing novel treatment options for areas of unmet patient need, particularly for diseases affecting children.”

The new treatment is a combination of 3 drugs -- elexacaftor, ivacaftor, and tezacaftor (Trikafta) -- that target the defective CFTR protein. It helps the protein made by the CFTR gene mutation function more effectively. Currently available therapies that target the defective protein are treatment options for some patients with cystic fibrosis, but many patients have mutations that are ineligible for treatment. This is the first approved treatment that is effective for patients wit cystic fibrosis with at least 2 F508del mutation.

The efficacy of the triple combination therapy in patients with cystic fibrosis aged 12 years and older was demonstrated in 2 trials. The first trial was a 24-week, randomised, double-blind, placebo-controlled trial in 403 patients who had an F508del mutation and a mutation on the second allele that results in either no CFTR protein or a CFTR protein that is not responsive to ivacaftor or tezacaftor plus ivacaftor. The second trial was a 4-week, randomised, double-blind, active-controlled trial in 107 patients who had 2 identical F508del mutations.

In each trial, the primary analysis looked at increases in the percent predicted forced expiratory volume in one second (ppFEV1), which is an established marker of cystic fibrosis lung disease progression. The triple combination treatment increased the ppFEV1 in both trials. In the first trial, it increased mean ppFEV1 13.8% from baseline compared with placebo. In the second trial, it increased mean ppFEV1 10% from baseline compared with tezacaftor plus ivacaftor. In the first trial, treatment with elexacaftor, ivacaftor, and tezacaftor also resulted in improvements in sweat chloride, number of pulmonary exacerbations, and body mass index compared with placebo.

Safety was based on data from the 510 patients in both trials. Serious adverse drug reactions that occurred more frequently in patients receiving elexacaftor, ivacaftor, and tezacaftor compared with placebo were rash and influenza events. The most common adverse events included headaches, upper respiratory tract infections, abdominal pains, diarrhoea, rashes, increased liver enzymes, nasal congestion, increased blood creatine phosphokinase, rhinorrhea, rhinitis, influenza, sinusitis, and increased blood bilirubin.

The prescribing information includes warnings related to elevated liver function tests (transaminases and bilirubin), use at the same time with other products that are inducers or inhibitors of Cytochrome P450 3A4 (CYP3A), and the risk of cataracts. Patients and their caregivers should speak with a healthcare professional about these risks and any medicines they take before starting treatment.

Reference: https://www.fda.gov/news-events/press-announcements/fda-approves-new-bre...

SOURCE: US Food and Drug Administration