RESEARCH SNAPSHOT
Kaftrio approval extended by EMA for cystic fibrosis from 6 years of age
Kaftrio triple therapy for use in patients with cystic fibrosis ( CF ) has now been extended to include children from 6 years of age .
Kaftrio has been given an extension to its existing marketing authorisation by the European Medicines Agency ( EMA ) for children as young as age 6 who have CF with at least one F508del mutation in combination with ivacaftor . 1
Kaftrio is combination therapy that contains 75mg ivacaftor , 50mg tezacaftor and 100mg elexacaftor . 2 The combination is already authorised in a regimen with ivacaftor 150mg tablets for the treatment of CF in patients aged 12 years and older who have at least one F508del mutation in the CF transmembrane conductance regulator ( CFTR ) gene .
CF is a rare and monogenic disease ( that is , caused by variation in a single gene ) which is thought to affect at least 100 000 people worldwide . 3 The condition is best described as a progressive , multi-organ disease that affects the lungs , liver , pancreas , GI tract , sinuses , sweat glands , and reproductive tract , and which leads to a reduced life expectancy . However , according to one report , 4 the life expectancy of children born today with CF is likely to surpass 50 years for the first time .
CF is due to mutations in the genes responsible for encoding of the cystic fibrosis transmembrane conductance regulator ( CFTR ) protein . 5 This defect results in reduced chloride secretion and increased sodium absorption through epithelial sodium channels and removal of water from secretions and which consequently become
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The three drugs present in Kaftrio work in combination . Ivacaftor functions as a potentiator of the CFTR protein for common gating mutations , allowing for an increase in chloride ion flow . Tezacaftor ensures correct folding and presentation of the mature CFTR protein to the cell surface , improving CFTR function for the F508del mutation . Elexacaftor also helps to ensure correct folding of the CFTR protein but acts at a different binding site to tezacaftor on the CFTR protein . As a result , the triple combination increases the function of the F508del mutated CFTR protein at the cell surface resulting in increased chloride ion transport and ultimately help hydrate and clear mucus from the airways .
Clinical data 6 already support the use of Kaftrio in children aged 12 years and over , although a more recent study 7 demonstrated the combination therapy was also effective in children from 6 years of age and enabled the EMA to extend its licensed usage . In addition to approval from the EMA , the Medicines and Healthcare products Regulatory Agency has also confirmed the same license extension for Kaftrio . 8
References 1 European Medicines Agency . Kaftrio . www . ema . europa . eu / en / medicines / human / summaries-opinion / kaftrio-1 ( accessed January 2022 ). 2 Kaftrio . Summary of Product Characteristics . www . medicines . org . uk / emc / product / 11724 / smpc # gref ( accessed January 2022 ). 3 Shteinberg M et al . Cystic Fibrosis . Lancet 2021 ; 397 ( 10290 ): 2195 – 211 . 4 Life Expectancy of CF children surpasses age 50 in UK for 1st time . Cystic Fibrosis news . https :// cysticfibrosisnewstoday . com / 2021 / 12 / 20 / life-expectancy-cf-children-surpasses-age-50- uk-1st-time / ( accessed January 2022 ). 5 Ridley K , Condren M . Elexacaftor-Tezacaftor-Ivacaftor : The first triple-combination cystic fibrosis transmembrane conductance regulator . J Pediatr Pharmacol Ther 2020 ; 25 ( 3 ): 192 – 7 . 6 Heijerman HGM et al . Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation : a double-blind , randomised , phase 3 trial . Lancet 2019 ; 394 ( 10212 ): 1940 – 8 . 7 Zemanick ET et al . A Phase 3 Open-Label Study of Elexacaftor / Tezacaftor / Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele . Am J Respir Crit Care Med 2021 ; 203 ( 12 ): 1522 – 32 . 8 “ Miracle ” cystic fibrosis treatment for children on the NHS . www . england . nhs . uk / 2022 / 01 / miracle-cystic-fibrosistreatment-for-children-on-the-nhs / ( accessed January 2022 ).
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