Drug updated on 9/4/2024
Dosage Form | Tablet (oral; 150 mg); Granule (oral; 5.8 mg, 13.4 mg, 25 mg, 50 mg, 75 mg) |
Drug Class | CFTR potentiators |
Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated for the treatment of cystic fibrosis (CF) in patients age 1 month and older who have at least one mutation in the CFTR gene that is responsive to ivacaftor based on clinical and/or in vitro assay data. If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of a CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use.
Latest News
Summary
- Kalydeco (ivacaftor) is indicated for the treatment of cystic fibrosis (CF) in patients age 1 month and older who have at least one mutation in the CFTR gene that is responsive to ivacaftor based on clinical and/or in vitro assay data. If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of a CFTR mutation, followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use.
- This summary is based on the review of 15 systematic review(s)/meta-analysis(es). [1-16]
- Lung Function (FEV1%): The triple combination elexacaftor-tezacaftor-ivacaftor (ETI) significantly improved FEV1% predicted, with increases of +10.47% (95% CI, 6.88-14.06) and up to 12.57% at 24 weeks. Dual therapies (lumacaftor-ivacaftor and tezacaftor-ivacaftor) showed improvements with mean differences ranging from 10.80% to 17.4%, but were less effective than ETI. Ivacaftor monotherapy showed no significant improvement in FEV1% for patients with F508del mutations.
- Quality of Life (QoL): ETI significantly improved quality of life scores, with one study reporting a +14.93 (95% CI, 9.98-19.89) increase and another showing a 21.46-point change in CFQ-R score at 4 weeks. Dual therapies also improved QoL scores but to a lesser extent compared to ETI.
- Pulmonary Exacerbations: ETI significantly reduced the number of acute pulmonary exacerbations, with a risk difference (RD) of -0.16 (95% CI, -0.28 to -0.04). Dual therapies also reduced exacerbation rates, with hazard ratios (HR) ranging from 0.61 to 0.70, but the reduction was smaller compared to ETI.
- Nutritional Status (BMI): ETI significantly improved BMI, with increases of +1.07 kg/m² (95% CI, 0.90-1.25) and 1.23 kg/m² (95% CI, 0.89-1.57) at 24 weeks. Dual therapies showed mixed results on BMI improvements, with smaller effects compared to ETI.
- ETI demonstrated a favorable safety profile with no significant difference in the overall incidence of adverse events compared to control groups (RD: -0.03, 95% CI: -0.08 to 0.01; overall AEs incidence: 0.824, 95% CI: 0.769-0.879; severe AEs incidence: 0.066, 95% CI: 0.028-0.104).
- Lumacaftor-ivacaftor was associated with specific adverse events, including early transient breathlessness and increased systolic and diastolic blood pressure in longer-term use. Additionally, respiratory-related adverse events were more frequently reported with this combination.
- A signal for mental health and neurocognitive adverse events was identified with all four CFTR modulators (ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, elexacaftor/tezacaftor/ivacaftor), indicating a need for further monitoring.
- Studies included various age groups (adults and adolescents aged ≥12 years, and children aged 6-11 years) and specific genotype subgroups (F508del homozygous, F508del/minimal function, and F508del/gating genotypes). Findings were generally consistent across different genotypes, with some variations in the magnitude of effectiveness.
Product Monograph / Prescribing Information
Document Title | Year | Source |
---|---|---|
Kalydeco (ivacaftor) Prescribing Information. | 2023 | Vertex Pharmaceuticals Incorporated, Boston, MA |