In line with previous predictions by CFI that the license for Kaftrio will likely be extended in future to cover more eligible people with CF in Ireland (and Europe), there is welcome news from Vertex.
The following news is a step towards the first announced extension of Kaftrio in Europe, although this particular extension still awaits final approval by the EMA, which will likely take another few months.
It is also likely that further possible extensions of Kaftrio will be announced in months to come as the result of the outcomes of current and future clinical trials, including for example the possible extension to children younger than 12 years of age, but these are considerations for the future. In short, and as previously advised by CFI, not everyone who has the potential to ultimately benefit from Kaftrio will gain immediate access to this drug therapy in the next few weeks, but there will likely be extensions of Kaftrio in months to come. It is further important to emphasise that the decision to access Kaftrio is one that can only be taken with your CF consultant and as with all drug therapies there are potential side effects that need to be fully considered.
It is further important to emphasise that not all people with CF can benefit from a CFTR drug therapy such as Kaftrio and there is a continuing need to explore other types of therapies, including for example gene-editing and gene therapy to ensure 'no-one left behind’.
News
Vertex today announced the European Medicines Agency (EMA) has validated a Type II Variation Marketing Authorization Application (MAA) for the expanded indication of KAFTRIO®* (ivacaftor/tezacaftor/elexacaftor) in combination with ivacaftor to treat CF in patients ages 12 years and older with at least one copy of the F508del mutation in the cystic fibrosis transmembrane conductance regulator(CFTR) gene.
If approved, eligible patients who have one copy of the F508del mutation and another CFTR mutation, such as a gating (F/G) or residual function (F/RF) mutation, will also be eligible for treatment. The MAA is supported by positive results from the global Phase 3 study (445-104) with KAFTRIO announced in July 2020. The application will now be reviewed by the Committee for Medicinal Products for Human Use (CHMP), which will issue an opinion to the European Commission regarding the potential approval for these patients.
KAFTRIO® (ivacaftor/tezacaftor/elexacaftor) in combination with ivacaftor is currently approved in Europe to treat people with CF ages 12 years and older with one F508del mutation and one minimal function mutation (F/MF), or two F508del mutations (F/F) in the CFTR gene.
Glossary of Terms
Marketing Authorisation Application (MAA) is an application submitted by a drug manufacturer seeking marketing authorisation, that is permission to bring a new medicine, or extension of a news medicine, to the market.
The Committee for Medicinal Products for Human Use (CHMP) is the most important sub-committee of the European Medicines Agency in respect of drug therapy approval.
CFTR Drug Therapies
Cystic Fibrosis (CF) is a life-shortening genetic disease affecting approximately 75,000 people worldwide and 1,400 people in Ireland. CF is a progressive, multi-system disease that affects the lungs, digestive system, liver sinuses, pancreas and other organs. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes, one from each parent, to have CF.
While there are many different types of CFTR mutations that can cause Cystic Fibrosis, the majority of all people with CF worldwide, including in Ireland, have at least one F508del mutation. These mutations lead to CF by creating non-working and/or too few CFTR proteins. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the build-up of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage.
CFTR drugs such as Kaftrio, Orkambi, Symdeco and Kalydeco are ground breaking because they treat the underlying cause of CF for the first time. However there is still a crucial place for other forms of drug therapy treatment for CF such as antibiotics; drugs that assist with food digestion and drugs that thin the thick, sticky mucus.