Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis

Aslam, Aisha; Jahnke, Nikki; Remmington, Tracey; Southern, Kevin W

doi:10.1016/j.prrv.2017.04.001

Cited by 20 publications

(19 citation statements)

References 2 publications

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“…The primary outcome was change in percentage predicted FEV1 with rate of pulmonary exacerbations as a secondary outcome. Overall there was no significant difference in mean relative change in FEV1 at 48 weeks between the treatment groups with a mean difference of 1.76% in favour of ataluren (95% CI -0.43, 3.95) 40,47 . The mean rate of pulmonary exacerbations was lower in the atalurentreated group compared to placebo (rate ratio 0.77; p=0.099) across the 48 weeks but this was not statistically significant.…”

Section: Phase III Studiesmentioning

confidence: 81%

Ataluren in cystic fibrosis: development, clinical studies and where are we now?

Abidin

Haq

Gardner

et al. 2017

Expert Opinion on Pharmacotherapy

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Cystic fibrosis (CF) is one of the most common genetically-acquired life-limiting conditions worldwide. The underlying defect is dysfunction of the cystic fibrosis transmembrane-conductance regulator (CFTR) which leads to progressive lung disease and other multi-system effects. Around 10% of people with CF have a class I nonsense mutation that leads to production of shortened CFTR due to a premature termination codon (PTC). Areas covered: We discuss the discovery of the small-molecule drug ataluren, which in vitro has been shown to allow read-through of PTCs and facilitate synthesis of full-length protein. We review clinical studies that have been performed involving ataluren in CF. Early-phase short-term cross-over studies showed improvement in nasal potential difference. A follow-up phase III randomised controlled trial did not show a significant difference for the primary outcome of lung function, however a post-hoc analysis suggested possible benefit in patients not receiving tobramycin. A further randomised controlled trial in patients not receiving tobramycin has been reported as showing no benefit but has not yet been published in full peer-reviewed form. Expert opinion: A small-molecule approach to facilitate read-through of PTCs in nonsense mutations makes intuitive sense. However, at present there is no high-quality evidence of clinical efficacy for ataluren in people with CF.

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Section: Phase III Studiesmentioning

confidence: 81%

Ataluren in cystic fibrosis: development, clinical studies and where are we now?

Abidin

Haq

Gardner

et al. 2017

Expert Opinion on Pharmacotherapy

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show abstract

“…A readthrough agent for CFTR class I mutation (Ataluren, PTC Therapeutics) showed potential benefits in vivo by increasing CFTR production and function; 173 however, it failed phase III clinical trial due to a lack of efficacy. 174 Channel modulators categorized into potentiators, correctors, and amplifiers have been used for CF treatment. Potentiators (ivacaftor, Kalydeco) can help in gating and conduction mutations by increasing the open probability of the CFTR channels.…”

Section: Asthmamentioning

confidence: 99%

Recent Developments in mRNA-Based Protein Supplementation Therapy to Target Lung Diseases

et al. 2019

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The lung has a very unique architecture to enable efficient transfer of oxygen and carbon dioxide required for oxidative metabolism. Inhaled gases travel through the airway tubes via trachea bronchi and bronchioles to the alveoli enriched with blood vessels, the primary site of gas exchange. Inflation and deflation of the lung is a prerequisite for gas exchange at the alveoli. This process requires multiple components like the extracellular matrix, smooth muscle cells, and cartilage for support and flexible collagen and the elastin fiber network for flexibility during inflation and deflation. Precisely regulated surface fluids, electrolytes, and mechanical activity of secretory

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“…Este ensayo se había iniciado en 2015 con pacientes con una mutación del grupo clase I. 5,6 Hasta la fecha, no hay medicamentos disponibles para la mutación clase I, la cual está presente en alrededor del 10 % de los pacientes con FQ. 5,6…”

Section: Agentes Read Throughunclassified

Moduladores CFTR (cystic fibrosis transmembrane conductance regulator): presente y futuro en la terapia de fibrosis quística. Revisión

2019

Arch Argent Pediat

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Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis

Cited by 20 publications

References 2 publications

Ataluren in cystic fibrosis: development, clinical studies and where are we now?

Ataluren in cystic fibrosis: development, clinical studies and where are we now?

Recent Developments in mRNA-Based Protein Supplementation Therapy to Target Lung Diseases

Moduladores CFTR (cystic fibrosis transmembrane conductance regulator): presente y futuro en la terapia de fibrosis quística. Revisión

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