Great news for many people with cystic fibrosis (CF) as NHS England agrees a deal for the three-drug combination therapy Kaftrio (Trikafta in the US). This comes just days after a positive opinion on Kaftrio was adopted by the Committee for Medicinal Products for Human Use (CHMP).

In negotiating the deal, NHS England has also ensured that equivalent terms will be offered to the health service systems in Northern Ireland, Scotland and Wales. 

There is currently no cure for CF but it is thought that Kaftrio could significantly improve the quality of life for up to 90% of people with the disease. This is a major improvement on the previously available therapies, which are suitable for around 50-55% of patients.

Kaftrio is particularly beneficial for people who produce little to no CFTR protein or CFTR proteins that are unresponsive to approved CFTR modulators. These are typically people with two copies of the most common mutation (F508del); or one F508del mutation and a further "minimal function mutation".

The F508del mutation impairs the folding of CFTR channels as they are produced inside the cell. This also causes them to "get stuck" inside the cell and not reach the cell membrane where they can perform their normal functions. When combined with other mutations, the detrimental impact of F508del on CFTR processing and function is exacerbated.

As the name suggests, Kaftrio is made up of three drugs: tezacaftor, elexacaftor and ivacaftor. This combination therapeutic improves the function of mutated CFTR channels by facilitating their folding and trafficking to the cell membrane, and enhancing the ability of the mutated channel to open (increasing the flow of ions through the channel). While not perfect, this restores some natural function and can significantly improve quality of life.

While there is still work to be done and a number of other promising therapies are in development, CHMP approval of Kaftrio and its adoption by the NHS is undoubtedly wonderful news for many CF patients.