What are the effects and side effects of kaftrio?

The effect of kaftrio

Kaftrio is a breakthrough therapy that is a combination of three medicines: elexacaftor, tezacaftor and ivacaftor. The combination of these three drugs in Kaftrio works synergistically to improve symptoms and quality of life in cystic fibrosis patients through different mechanisms. It is suitable for the treatment of cystic fibrosis (CF) patients aged 2 years and above. It improves the patient's survival rate, prolongs the survival period, and improves the patient's quality of life. Elexacaftor and tezacaftor work by increasing the amount of mature CFTR protein on the cell surface. It can improve the function of ion channels, thereby alleviating the symptoms of patients. Ivacaftor is known as a CFTR potentiator, and its role is to promote the CFTR protein across the cell membrane and improve its ability to transport salt and water. This helps hydrate and clear mucus from the respiratory tract, reducing obstruction of the respiratory tract by thick mucus, thereby improving respiratory function.

kaftrio side effects

Common symptoms of kaftrio include headache, upper respiratory tract infection, abdominal pain, diarrhea, rash, nasal congestion, rhinorrhea, rhinitis, influenza, sinusitis, increased alanine aminotransferase, creatine phosphokinase, aspartate aminotransferase, blood bilirubin, etc. The patient's physique and condition are different, and the side effects after taking the drug are also different.

The experimental results of kaftrio

In a phase 2 study of cystic fibrosis patients homozygous for the F508del mutation, the addition of the next-generation CFTR corrector elexacaftor (VX-445) to tezacaftor plus ivacaftor further improved the function and clinical outcomes of F508del CFTR.

A Phase 3, multicenter, randomized, double-blind, active-controlled trial (NCT03525548) of elexacaftor plus tezacaftor plus ivacaftor was conducted at 44 sites in 4 countries. Eligible participants were cystic fibrosis patients homozygous for the F508del mutation, 12 years of age or older, stable disease, and a percent predicted forced expiratory volume in 1 second (ppFEV1) of 40-90% inclusive.

After a 4-week tezacaftor plus ivacaftor run-in period, participants were randomized (1:1) to 4 weeks of elexacaftor 200 mg once daily plus tezacaftor 100 mg once daily plus ivacaftor 150 mg every 12 hours, or 100 mg of tezacaftor plus 150 mg of ivacaftor orally every 12 hours for 4 weeks.

The primary outcome was the absolute change from baseline in ppFEV1 at week 4 (measured at the end of the tezacaftor plus ivacaftor run-in). Key secondary outcomes were absolute changes in sweat chloride and Cystic Fibrosis Questionnaire-Respiratory Domain (CFQ-RD) score.

Research results:

A total of 113 participants participated. After run-in, 107 participants were randomly assigned (55 to the elexacaftor plus tezacaftor plus ivacaftor group and 52 to the tezacaftor plus ivacaftor group) and completed the 4-week treatment period. The elexacaftor plus tezacaftor plus ivacaftor group improved the primary outcome of ppFEV1 (least squares mean [LSM] treatment difference, 10.0 percentage points) and the key secondary outcomes sweat chloride concentration (LSM treatment difference, -45.1 mmol/L), and CFQ-R RD score (LSM treatment difference compared with tezacaftor plus ivacaftor, 17.4 points). The triple regimen (kaftrio) was well tolerated without interruption.

Conclusion

Elexacaftor plus tezacaftor plus ivacaftor (i.e., kaftrio) provides robust clinical benefits compared to tezacaftor plus ivacaftor alone, has a favorable safety profile, and shows the potential to bring transformative improvements in the lives of cystic fibrosis patients homozygous for the F508del mutation.

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References

Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS; VX17-445-103 Trial Group. 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, randomized, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1940-1948. doi: 10.1016/S0140-6736(19)32597-8. Epub 2019 Oct 31. Erratum in: Lancet. 2020 May 30;395(10238):1694. PMID: 31679946; PMCID: PMC7571408.