History
Lumacaftor/ivacaftor was approved by the FDA in July 2015 under breakthrough therapy status and under a priority review. Previously approved for adults and pre-teens, approved on 8-7-18 for children age 2–5. Society and culture
As of March 2016 the combination drug cost $259,000 a year in the United States.In Denmark, it was estimated in August 2015 that if the drug were introduced, the cost would amount to 2 million Danish krones (approximately 270,000 euro) each year per person.The Dutch Minister of Health announced in October 2017 that the drug would not be admitted to the public health insurance package, making it impossible to have treatment with the drug covered by Dutch health insurance. The minister stated that the price for the drug, negotiated to 170,000 euro per patient per year, is "unacceptably high in relation to the relatively modest effect, as determined by the (Dutch) Healthcare Institute". Approximately 750 patients are affected by this decision. On 25 October, the Dutch Minister of Health announced that an agreement had been brokered with Vertex Pharmaceuticals, the company that manufactures the drug, resulting in admittance to the Dutch public health insurance package. Part of the agreement is that the result of the negotiation about the price of the treatment will not be disclosed.Protracted discussions within the United Kingdom were brought to a conclusion in September and October 2019 as NHS Scotland and NHS England both struck deals with Vertex respectively.
The medication also does not appear to change a persons quality of life or the number of times a year a person has a worsening of lung function. Effects on life expectancy are unclear. Side effects
Some people taking the combination drug had elevated transaminases; the combination drug should be used with caution for people with advanced liver disease and liver function should be measured for the first three months for all people starting the combination drug.People starting the combination have respiratory discomfort, and some children taking the combination drug developed cataracts.Lumacaftor/ivacaftor may interfere with hormonal contraceptives. Dosage of the combination drug should be reduced if the person is taking a drug that inhibits CYP3A, and inducers of CYP3A should not be used concomitantly. Mechanism of action
F508del is a mutation that causes the CFTR protein to misfold and cells destroy such proteins soon after they are made; lumacaftor acts as a chaperone during protein folding and increases the number of CFTR proteins that are trafficked to the cell surface. Ivacaftor is a potentiator of CFTR that is already at the cell surface, increasing the probability that the defective channel will be open and allow chloride ions to pass through the channel pore. The two drugs have synergistic effects. Physical properties
Each of lumacaftor and ivacaftor is a white to off-white powder that is practically insoluble in water. The combination drug is a single pill containing 200 mg of lumacaftor and 125 mg of ivacaftor.