Rare Daily Staff

The U.S. Food and Drug Administration has approved Vertex Pharmaceuticals’ triple combination drug Trikafta for the treatment of a specific form of rare respiratory disease cystic fibrosis in people ages 12 years and older.

Trikafta is indicated for people who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the most common genetic mutation underlying the disease.

Cystic fibrosis (CF) is a rare, life-shortening genetic disease. It is caused by mutations in the CFTR gene that lead to a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) protein. Children must inherit two defective CFTR genes—one from each parent—to have CF. There are approximately 2,000 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic test, lead to CF 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 early 30s.

The speedy approval, just two months after submission, adds a fourth FDA-approved cystic fibrosis drug in Vertex’s arsenal.

“The incredible speed of this approval underscores our shared sense of urgency with the FDA and the CF community for bringing this medicine to eligible people with CF, particularly those without a medicine targeting the underlying cause of their disease,” said Reshma Kewalramani, executive vice president, global medicines development and medical affairs and chief medical officer at Vertex.

Trikafta is designed to increase the quantity and function of the F508del-CFTR protein at the cell surface. Approval was based on positive results of two global phase 3 studies: a 24-week phase 3 study in people with one F508del mutation and one minimal function mutation and a 4-week phase 3 study in people with two F508del mutations. Both phase 3 studies showed statistically significant improvements in lung function, which was the primary endpoint, and in all key secondary endpoints. In these studies, the triple combination regimen was generally well tolerated.

Trikafta is the first approved triple combination therapy for patients 12 years and older with the most common cystic fibrosis mutation, representing an estimated 90 percent of the cystic fibrosis population—about 27,000 people in the United States, according to the FDA.

“Today’s approval is a historic moment in cystic fibrosis care, with the potential for more people to benefit from CFTR modulator therapy to treat the basic defect of their disease,” said Steven Rowe, director, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham.

Vertex’s triple combination therapy is under review by the European Medicines Agency, and is currently being evaluated in children ages six through eleven in a phase 3 study.

Photo: Reshma Kewalramani, executive vice president, global medicines development and medical affairs and chief medical officer at Vertex

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