kaftrio(Trikafta)治疗囊性纤维化的效果好吗？

kaftrio (Trikafta) is effective in treating cystic fibrosis and can significantly improve lung function, reduce lung deterioration and improve quality of life. In multinational Phase II and III studies, kaftrio (Trikafta) improved lung function and respiratory-related quality of life compared with a comparator (placebo or ivacaftor/tezacaftor).

kaftrio(Trikafta)

It is a cystic fibrosis transmembrane regulator (CFTR) modulator. In October 2019, the US FDA approved elexacaftor/ivacaftor/tezacaftor for the treatment of cystic fibrosis in patients aged ≥ 12 years old with ≥ 1 F508del mutation in the CFTR gene. The EU is conducting regulatory evaluation of elexacaftor/ivacaftor/tezacaftor as a cystic fibrosis treatment drug.

kaftrio (Trikafta) for the treatment of cystic fibrosis

kaftrio (Trikafta) increases CFTR channel activity and improves lung function in CF patients aged 6 years and older with the G551D-CFTR gated mutation.

Lumacaftor/ivacaftor (Orkambi) is a fixed-dose tablet containing a corrector (Lumacaftor) and a potentiator (ivacaftor) of the cystic fibrosis transmembrane conductance regulator (CFTR) and is the first therapy approved to treat the underlying cause of cystic fibrosis in patients (age ≥12 years) who are homozygous for the most common CFTR mutation, F508del.

Lumacaftor improves F508del CFTR processing and its transport to the cell surface, while ivacaftor increases channel opening probability and chloride transport.

In two 24-week trials in approved patient populations (traffic and transportation), kaftrio 400 mg plus ivacaftor 250 mg (dose every 12 hours) in combination with standard of care demonstrated statistically significant improvements in lung function (measured as percent predicted forced expiratory volume in 1 second) of approximately 3% compared with placebo.

Lumacaftor plus ivacaftor did not significantly improve respiratory symptoms but reduced lung exacerbations to a clinically meaningful degree and, in one trial (Transport), significantly improved body mass index (BMI).

In an ongoing extension of these studies (PROGRESS), lumacaftor plus ivacaftor provided clinical benefit over 72 weeks of treatment.

Lumacaftor plus ivacaftor had acceptable tolerability, most commonly in the respiratory or gastrointestinal tract. Lumacaftor/ivacaftor expands treatment options for cystic fibrosis patients homozygous for the F508del-CFTR mutation.

In a study evaluating 403 CF patients (200 kaftrio, 203 placebo) aged 12 years and older, the primary endpoint at the interim analysis was the mean absolute change in ppFEV1 from baseline at week 4.

Among the 403 patients included in the interim analysis, the treatment difference between TRIKAFTA and placebo was 13.8% in mean absolute change from baseline in ppFEV1 at week 4. The treatment difference in mean absolute change in ppFEV1 between kaftrio and placebo was 14.3% from baseline to week 24, with mean improvements in ppFEV1 observed at the first assessment on day 15 and sustained through the 24-week treatment period.

There are some risks during the use of Trikafta, such as elevated transaminase and liver damage, allergic reactions, cataracts, etc. At the same time, combined use with CYP3A inducers or CYP3A inhibitors will reduce the drug efficacy of Trikafta, and it needs to be used under the guidance of a doctor.

References:

Deeks ED. Lumacaftor/Ivacaftor: A Review in Cystic Fibrosis. Drugs. 2016 Aug;76(12):1191-201. doi: 10.1007/s40265-016-0611-2. PMID: 27394157.

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