Ivacaftor, lumacaftor and tezacaftor
In 2012 ivacaftor was designated as an orphan drug, identifying cystic fibrosis as affecting fewer than 200,000 people in the United States. On 31 January 2012, Vertex gained FDA approval[22] of the first drug, Kalydeco,[23] to treat the underlying cause of cystic fibrosis rather than the symptoms, in patients 6 years or older who have the G551D gene mutation.
In the US, 30,000 people have cystic fibrosis. About 4% of those, or 1,200, have the G551D gene mutation. In 2017 Vertex marketed the drug for $311,000 per person per year.[24][25]
Vertex also studied ivacaftor in combination with another drug (lumacaftor[26]) for the most common mutation in cystic fibrosis (CF), known as F508del, and published the first set of results in 2012. Vertex produced the drug after 13 years of research and development, with $70 million in support from the Cystic Fibrosis Foundation.[27][28]
In the UK, the company provided the drug free for a limited time for certain patients. Subsequently, the hospitals decided to continue to pay for the drug for those patients. UK agencies estimated the cost per quality adjusted life year (QALY) at between £335,000 and £1,274,000—far above the NICE thresholds[29] of £20,000-£30,000.
On 5 November 2014 Vertex announced the submission of a New Drug Application (NDA) to the FDA for a fully co-formulated combination of lumacaftor and ivacaftor for people with cystic fibrosis ages 12 and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.[30] In 2015, FDA approved the combination of lumacaftor and ivacaftor to treat CF in patients 12 years and older, who have the F508del mutation. The combination drug is marketed under the tradename Orkambi.[31]
On 28 March 2017, Vertex announced Phase 3 data from a dual combination treatment, tezacaftor plus ivacaftor, in patients with cystic fibrosis.[32] On 12 February 2018, the FDA approved the combination, marketed as Symdeko.[33]
Triple combination treatments
In 2016, Vertex began developing a new group of CFTR modulators in combination with tezacaftor and ivacaftor.[33] In 2017, the company reported results that showed benefits for patients with different mutations that represent 90% of the CF population.[34] On 22 October 2019, two months after a new drug application was filed with it, the FDA approved Vertex's Triple-combo therapy Trikafta (elexacaftor/tezacaftor/ivacaftor) for patients 12 and older with at least one F508del mutation.[35] The FDA approval covers approximately 90% of patients with cystic fibrosis.[36]
Vertex has refused to make Trikafta available in developing countries and works to block generic alternatives, making it inaccessible for thousands of patients.[37]
