Advancing clinical development pathways for new CFTR modulators in cystic fibrosis
Autor: | Donald R. VanDevanter, Nicole Mayer-Hamblett, Michael P. Boyle |
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Rok vydání: | 2016 |
Předmět: |
Pulmonary and Respiratory Medicine
Cystic Fibrosis Genotype Rare lung diseases Regulator Aminopyridines Cystic Fibrosis Transmembrane Conductance Regulator Review Disease Quinolones Pharmacology Aminophenols Bioinformatics Cystic fibrosis 03 medical and health sciences 0302 clinical medicine Humans Medicine Benzodioxoles Molecular Targeted Therapy 030212 general & internal medicine Randomized Controlled Trials as Topic Clinical Trials as Topic biology business.industry Cftr proteins Genetic Therapy medicine.disease Cystic fibrosis transmembrane conductance regulator 3. Good health Clinical trial Drug Combinations Treatment Outcome 030228 respiratory system Drug development Mutation Critical Pathways Quality of Life biology.protein Biomarker (medicine) business Biomarkers |
Zdroj: | Thorax |
ISSN: | 1468-3296 0040-6376 |
Popis: | Cystic fibrosis (CF) is a life-shortening genetic disease affecting approximately 70 000 individuals worldwide. Until recently, drug development efforts have emphasised therapies treating downstream signs and symptoms resulting from the underlying CF biological defect: reduced function of the CF transmembrane conductance regulator (CFTR) protein. The current CF drug development landscape has expanded to include therapies that enhance CFTR function by either restoring wild-type CFTR protein expression or increasing (modulating) the function of mutant CFTR proteins in cells. To date, two systemic small-molecule CFTR modulators have been evaluated in pivotal clinical trials in individuals with CF and specific mutant CFTR genotypes that have led to regulatory review and/or approval. Advances in the discovery of CFTR modulators as a promising new class of therapies have been impressive, yet work remains to develop highly effective, disease-modifying modulators for individuals of all CF genotypes. The objectives of this review are to outline the challenges and opportunities in drug development created by systemic genotype-specific CFTR modulators, highlight the advantages of sweat chloride as an established biomarker of CFTR activity to streamline early-phase development and summarise options for later phase clinical trial designs that respond to the adoption of approved genotype-specific modulators into standard of care. An optimal development framework will be needed to move the most promising therapies efficiently through the drug development pipeline and ultimately deliver efficacious and safe therapies to all individuals with CF. |
Databáze: | OpenAIRE |
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