Considerations for the use of lumacaftor and ivacaftor fixed dose combination oral tablets (OrkambiTM) for the management of persons with cystic fibrosis and two F508del CFTR mutations
ثبت نشده
چکیده
Executive Summary The lumacaftor and ivacaftor fixed dose combination oral tablet (OrkambiTM, Vertex Pharmaceuticals, Inc.) is the second Food and Drug Administration (FDA) approved member of a new pharmacologic class of drugs termed cystic fibrosis transmembrane conductance regulator (CFTR) modulators.[1] CFTR modulators target the underlying defect (reduced CFTR function) that causes disease sequelae (Figure 1) and are fundamentally different from other chronic cystic fibrosis (CF) treatments that address the ‘downstream’ complications and clinical manifestations of CF.
منابع مشابه
Two Small Molecules Restore Stability to a Subpopulation of the Cystic Fibrosis Transmembrane Conductance Regulator with the Predominant Disease-causing Mutation*
Cystic fibrosis (CF) is caused by mutations that disrupt the plasma membrane expression, stability, and function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Two small molecules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used clinically to treat CF, although some studies suggest that they have counteracting effects on CFTR stability. ...
متن کاملLumacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease homozygous for F508del-CFTR.
OBJECTIVE Evaluation of the safety, tolerability, and efficacy of lumacaftor/ivacaftor in patients with cystic fibrosis (CF) with severe lung disease. METHODS Patients with CF 12 years of age and older, homozygous for F508del-CFTR, with percent predicted forced expiratory volume in 1 second (ppFEV1) <40 received lumacaftor 400 mg/ivacaftor 250mg every 12h (full dose) for 24weeks in an open-la...
متن کاملA new chapter in therapy for cystic fibrosis.
In the New England Journal of Medicine, Wainwright and colleagues reported the results of two phase 3 studies to assess the eff ects of a combination of lumacaftor and ivacaftor for the treatment of cystic fibrosis; specifi cally, in patients homozygous for the most common mutation in the gene encoding the cystic fi brosis transmembrane regulator (CFTR) protein, Phe508del. Although cystic fibro...
متن کاملMeasurements of Functional Responses in Human Primary Lung Cells as a Basis for Personalized Therapy for Cystic Fibrosis
BACKGROUND The best investigational drug to treat cystic fibrosis (CF) patients with the most common CF-causing mutation (F508del) is VX-809 (lumacaftor) which recently succeeded in Phase III clinical trial in combination with ivacaftor. This corrector rescues F508del-CFTR from its abnormal intracellular localization to the cell surface, a traffic defect shared by all Class II CFTR mutants. Our...
متن کاملFatty Acid Cysteamine Conjugates as Novel and Potent Autophagy Activators That Enhance the Correction of Misfolded F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
A depressed autophagy has previously been reported in cystic fibrosis patients with the common F508del-CFTR mutation. This report describes the synthesis and preliminary biological characterization of a novel series of autophagy activators involving fatty acid cysteamine conjugates. These molecular entities were synthesized by first covalently linking cysteamine to docosahexaenoic acid. The res...
متن کامل