ABCMdb

PMID: 26091951

Barry PJ, Jones AM
New and Emerging Treatments for Cystic Fibrosis.
Drugs. 2015 Jul;75(11):1165-75. doi: 10.1007/s40265-015-0424-8., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Gly551Asp LEADING ARTICLE New and Emerging Treatments for Cystic Fibrosis Peter J. Barry1 ߦ Andrew M. Jones1 Published online: 20 June 2015 &#d3; Springer International Publishing Switzerland 2015 Abstract Recently, a significant number of additional key medications have become licensed in Europe for the treatment of patients with cystic fibrosis (CF), including a number of inhaled antibiotics, such as nebulised aztreonam and dry powder versions of colistin and tobramycin for inhalation; dry powder inhaled mannitol, an agent to improve airway hydration and aid airway clearance; and ivacaftor, an oral therapy that directly acts on dysfunctional CFTR to correct the basic defect encountered in CF patients with the G551D CF gene mutation. Login to comment 1 ABCC7 p.Gly551Asp The marked success of ivacaftor both in clinical trials and in post-licensing evaluation studies in treating patients with G551D and other gating mutations has greatly encouraged the ongoing development of similar therapies that can directly target the underlying cause of CF. Login to comment 43 ABCC7 p.Gly551Asp In a landmark phase III placebo-controlled trial in adult and adolescent CF patients carrying the G551D mutation, ivacaftor therapy resulted in a significant improvement in lung function (10.6 % absolute difference in FEV1), a significant reduction in pulmonary exacerbations and a significant increase in weight [11]. Login to comment 54 ABCC7 p.Gly551Asp A multi-centre retrospective study of patients with severe lung disease who carried the G551D mutation and received ivacaftor therapy on a compassionate use programme demonstrated improvements in lung function and weight and, perhaps most importantly, significant reductions in time spent receiving intravenous antibiotics [22]. Login to comment 55 ABCC7 p.Gly551Asp The success of ivacaftor therapy in patients carrying the G551D mutation has led to its study in patients who carry other class III mutations. Login to comment 58 ABCC7 p.Gly970Arg Improvements were seen for patients with all mutations with the exception of G970R, leading to licensing of ivacaftor for a further eight mutations. Login to comment 59 ABCC7 p.Gly970Arg The finding of G970R as an outlier merits further investigation due to strong pre-clinical data suggesting this mutation would be responsive to CFTR potentiation. Login to comment 60 ABCC7 p.Gly551Asp The KIWI study was an open-label study to assess the safety and pharmacokinetics of ivacaftor in children aged 2-5 years who carried either G551D or another class III mutation [24]. Login to comment 68 ABCC7 p.Arg117His Class IV mutations (e.g. R117H) represent mutations that lead to the production of CFTR protein, which demonstrate altered conductance, a qualitative defect. Login to comment 69 ABCC7 p.Arg117His Part of this qualitative defect in the mutation R117H has been attributed to 'gating` problems similar to class III mutations, and highlighting the complexities of classifying individual mutations. Login to comment 70 ABCC7 p.Arg117His KONDUCT was a randomised double-blind, placebo-controlled trial of ivacaftor therapy in patients expressing the R117H mutation [26]. Login to comment 172 ABCC7 p.Gly551Asp If superiority of a new therapy is a potential goal, the requirement for withdrawal of clearly effective therapies such as ivacaftor in patients carrying the G551D mutation may limit the development of some agents. Login to comment