Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del <i>CFTR</i>

Rehman, Abdul; Baloch, Noor Ul-Ain; Janahi, Ibrahim A.

doi:10.1056/nejmc1510466

Cited by 126 publications

(62 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results of safety and tolerability analyses in the PROGRESS extension study indicated that adverse events were similar to what was observed during the first 24 weeks of the study, with the most commonly observed events including shortness of breath, chest tightness, viral infection of the upper respiratory tract, and gastrointestinal symptoms, as listed in adverse events tables of the phase 2 and phase 3 trials [49, 52]. An observational study, PROSPECT, is ongoing and focuses on examining biomarkers of CFTR function and banking of specimens.…”

Section: Post-marketing Surveillancementioning

confidence: 85%

“…Based on the phase 2 results, two phase 3 clinical trials, TRAFFIC and TRANSPORT, were conducted using a combination of lumacaftor (600 mg daily or 400 mg twice daily) and ivacaftor (250 mg twice daily) in patients 12 years and older homozygous for the F508del-CFTR mutation [52], summarized in Table 2. Both trials met their primary outcome measure of statistically significant improvement in FEV 1 , although the increase of 2.6–4% [52] were modest and significantly below those observed with ivacaftor in CF patients with gating mutations (10.6–12.5%) [15, 54].…”

Section: Clinical Efficacymentioning

confidence: 99%

“…Both trials met their primary outcome measure of statistically significant improvement in FEV 1 , although the increase of 2.6–4% [52] were modest and significantly below those observed with ivacaftor in CF patients with gating mutations (10.6–12.5%) [15, 54]. The TRAFFIC and TRANSPORT studies did show significant reduction in pulmonary exacerbations as an important secondary outcome measure, as well as other secondary measures including the Cystic Fibrosis Questionnaire-Revised (CFQ-R) quality of life respiratory scale and body mass index.…”

Section: Clinical Efficacymentioning

confidence: 99%

See 2 more Smart Citations

Efficacy of lumacaftor-ivacaftor for the treatment of cystic fibrosis patients homozygous for the F508del-CFTR mutation

Cholon

Esther

Gentzsch

2016

Expert Review of Precision Medicine and Drug Development

View full text Add to dashboard Cite

Cystic fibrosis (CF) results from mutations in the CF transmembrane conductance regulator (CFTR) gene, which codes for the CFTR channel protein. The most common mutation in CF is F508del, which produces a misfolded protein with diminished channel activity. The development of small-molecule CFTR-modulator compounds offers an exciting and novel approach for pharmacological treatment of CF. The corrector lumacaftor helps rescue F508del-CFTR to the cell surface, and potentiator ivacaftor increases F508del-CFTR channel activity. The combination of lumacaftor-ivacaftor (Vertex Pharmaceuticals Incorporated) represents the first FDA-approved therapy for CF patients with two copies of the F508del mutation. Although this combination therapy is the first treatment to directly target the F508del-CFTR mutation, patients taking this drug displayed only modest improvements in lung function. This article summarizes recent data from clinical trials and research discoveries relating to the lumacaftor-ivacaftor treatment, and considers options for identifying future therapies that will be most efficacious for all CF patients.

show abstract

Section: Post-marketing Surveillancementioning

confidence: 85%

Section: Clinical Efficacymentioning

confidence: 99%

Section: Clinical Efficacymentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of lumacaftor-ivacaftor for the treatment of cystic fibrosis patients homozygous for the F508del-CFTR mutation

Cholon

Esther

Gentzsch

2016

Expert Review of Precision Medicine and Drug Development

View full text Add to dashboard Cite

show abstract

“…The drug Lumacaftor was shown to improve CFTR F508del protein folding. Clinical trials are now in place that use combined treatment with Ivacaftor and Lumacaftor to ensure passage of CFTRf508del to the cell surface and Ivacaftor to facilitate CFTR channel protein on the cell surface (Rehman et al, 2015). …”

Section: Precision and Personalized Medicinementioning

confidence: 99%

DNA Sequence Analysis in Clinical Medicine, Proceeding Cautiously

Smith

2017

Front. Mol. Biosci.

View full text Add to dashboard Cite

Delineation of underlying genomic and genetic factors in a specific disease may be valuable in establishing a definitive diagnosis and may guide patient management and counseling. In addition, genetic information may be useful in identification of at risk family members. Gene mapping and initial genome sequencing data enabled the development of microarrays to analyze genomic variants. The goal of this review is to consider different generations of sequencing techniques and their application to exome sequencing and whole genome sequencing and their clinical applications. In recent decades, exome sequencing has primarily been used in patient studies. Discussed in some detail, are important measures that have been developed to standardize variant calling and to assess pathogenicity of variants. Examples of cases where exome sequencing has facilitated diagnosis and led to improved medical management are presented. Whole genome sequencing and its clinical relevance are presented particularly in the context of analysis of nucleotide and structural genomic variants in large population studies and in certain patient cohorts. Applications involving analysis of cell free DNA in maternal blood for prenatal diagnosis of specific autosomal trisomies are reviewed. Applications of DNA sequencing to diagnosis and therapeutics of cancer are presented. Also discussed are important recent diagnostic applications of DNA sequencing in cancer, including analysis of tumor derived cell free DNA and exosomes that are present in body fluids. Insights gained into underlying pathogenetic mechanisms of certain complex common diseases, including schizophrenia, macular degeneration, neurodegenerative disease are presented. The relevance of different types of variants, rare, uncommon, and common to disease pathogenesis, and the continuum of causality, are addressed. Pharmogenetic variants detected by DNA sequence analysis are gaining in importance and are particularly relevant to personalized and precision medicine.

show abstract

“…1 Individuals with orphan conditions have played an active role not only in improving care of their own condition but often in improving the care of individuals with more common conditions by participating in clinical trials, donating biospecimens, and even through advocacy. Nowhere has this been more evident recently than in the field of lipidology, where the study of orphan conditions such as homozygous familial hypercholesterolemia, a rare condition generally caused by biallelic mutations in LDLR, or lysosomal acid lipase deficiency 2 has led to the Food and Drug Administration approval of specifically targeted therapies (lomitapide, mipomersen and the PCSK9 inhibitor evolocumab for the former, and sebelipase alfa for the latter).…”

mentioning

confidence: 99%

Standards of Evidence and Mechanistic Inference in Autosomal Recessive Hypercholesterolemia

Priest

Knowles

2016

ATVB

View full text Add to dashboard Cite

Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR

Cited by 126 publications

References 19 publications

Efficacy of lumacaftor-ivacaftor for the treatment of cystic fibrosis patients homozygous for the F508del-CFTR mutation

Efficacy of lumacaftor-ivacaftor for the treatment of cystic fibrosis patients homozygous for the F508del-CFTR mutation

DNA Sequence Analysis in Clinical Medicine, Proceeding Cautiously

Standards of Evidence and Mechanistic Inference in Autosomal Recessive Hypercholesterolemia

Contact Info

Product

Resources

About