Drug updated on 9/4/2024
Dosage Form | Tablet (oral; lumacaftor/ivacaftor: 100/125 mg, 200/125 mg); Granules (oral; lumacaftor/ivacaftor: 75/94 mg, 100/125 mg, 150/188 mg) |
Drug Class | CFTR potentiators |
Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated for the treatment of cystic fibrosis (CF) in patients age aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene.
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Summary
- Orkambi (lumacaftor/ivacaftor) is indicated for the treatment of cystic fibrosis (CF) in patients aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene.
- This summary is based on the review of five systematic review(s)/meta-analysis(es). [1-5]
- Lumacaftor/Ivacaftor (LUM/IVA): Dual therapy improved FEV1 % predicted compared to placebo, with meta-analysis showing a mean difference (MD) of 2.38 (1.62-3.15, P<0.00001); triple therapy demonstrated greater relative and absolute changes in FEV1 % predicted, and significant improvement in BMI (MD 0.21, 0.03-0.39, P=0.02).
- Tezacaftor/Ivacaftor (TEZ/IVA): Dual therapy improved FEV1 % predicted compared to placebo at all time points, with significant improvements in ppFEV1 in meta-analysis (P=0.002); no reported increases in blood pressure in RCTs.
- Elexacaftor-Tezacaftor-Ivacaftor (ELX/TEZ/IVA): Triple therapy resulted in greater relative and absolute changes in FEV1 % predicted, significant improvements in BMI, and little to no difference in adverse events compared to control in individuals 12 years and older.
- LUM/IVA: Higher frequency of respiratory-related adverse events (AEs) and discontinuations were observed in real-world studies, with RCTs showing increased respiratory AEs compared to placebo, including early transient breathlessness and increased systolic and diastolic blood pressure over 120 weeks. Meta-analysis revealed an increased proportion of discontinued treatments due to AEs (OR 2.71, 1.3-5.63, P=0.008).
- TEZ/IVA: No significant impact on the number of participants reporting AEs in meta-analysis (P=0.53); RCTs reported no increases in blood pressure and one death deemed unrelated to the study drug.
- Treatment effects varied significantly by genotype, particularly for F508del, G551D, and R117H mutations, and age-specific outcomes showed differing effectiveness and safety profiles, especially noting a lack of data in children under 12 years for some therapies. Differences were also observed between real-world studies and RCTs in the frequency and types of adverse events reported.
Product Monograph / Prescribing Information
Document Title | Year | Source |
---|---|---|
Orkambi (lumacaftor and ivacaftor) Prescribing Information. | 2023 | Vertex Pharmaceuticals Incorporated., Boston, MA |
Systematic Reviews / Meta-Analyses
Document Title | Year | Source |
---|---|---|
Real-world safety of CFTR modulators in the treatment of cystic fibrosis: a systematic review. | 2021 | Journal of Clinical Medicine |
Effect of CFTR modulators on anthropometric parameters in individuals with cystic fibrosis: an evidence analysis center systematic review. | 2020 | Journal of the Academy of Nutrition and Dietetics |
Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). | 2020 | The Cochrane Database of Systematic Reviews |
Efficacy and safety of CFTR corrector and potentiator combination therapy in patients with cystic fibrosis for the f508del-cftr homozygous mutation: a systematic review and meta-analysis. | 2019 | Advances in Therapy |
A systematic review of the clinical efficacy and safety of CFTR modulators in cystic fibrosis. | 2019 | Scientific Reports |
Clinical Practice Guidelines
Document Title | Year | Source |
---|---|---|
Brazilian guidelines for the pharmacological treatment of the pulmonary symptoms of cystic fibrosis. Official document of the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association). | 2023 | Brazilian Journal of Pulmonology |