Vertex Pharmaceuticals has won the US Food and Drug Administration’s approval to start selling its triple-combination treatment Trikafta for cystic fibrosis (CF), extending the reach of the company’s CF drugs to 90% of patients with the disease.

CF is a life-shortening multi-system genetic disease, caused by a defective version of the CFTR chloride channel that leads to problems in the lungs, pancreas, gastrointestinal tract, sweat glands and other organs. Common mutations that cause CF include Phe508del, carried by around 90% of patients in the United States, and give rise to CFTR proteins that are misfolded, that can get trapped in the endoplasmic reticulum, and that are not fully functional when they do traffic to the cell surface. Vertex has long been working on therapeutics to correct the shape of the protein to allow it to better traffic to the cell surface (‘correctors’) and to activate its function by holding it open at the cell surface (‘potentiators’). Trikafta combines ivacaftor, tezacaftor and elexacaftor. Ivacaftor was first approved as the monotherapy Kalydeco by the FDA in 2012 and is a ‘potentiator’ that helps keep mutated CFTR in an open state. At that time, however, it was only approved for around 5% of cystic fibrosis patients. Tezacaftor is a ‘corrector’, approved in 2018 in a combination with ivacaftor sold as Symdeko. By combining ivacaftor and tezacaftor with another ‘corrector’, elexacaftor, the company has improved the reach and efficacy of its cystic fibrosis drugs.

Elexacaftor, the newest corrector and a key component of Trikafta, went from first synthesis to combination approval in the record-breaking time of under four years, says Reshma Kewalramani, chief medical officer at Vertex and incoming CEO. “It really does sound unbelievable, but it is true,” she adds.

Vertex anticipates $3.7 billion in sales from its CF portfolio in 2019. The $300,000-plus annual price tag for these drugs frequently draws fire, however. The Cystic Fibrosis Foundation, which backed and profited from the discovery and development of Vertex’s CF candidates, has set up a research agenda to find drugs for the 10% of patients who don’t benefit from available options, which includes work on mRNA-based drugs, gene replacement therapies and gene editing treatments.