Ataluren/ivacaftor combination therapy: Two N-of-1 trials in cystic fibrosis patients with nonsense mutations.
Jacelyn E Peabody LeverVenkateshwar MutyamHeather Y HathorneNing PengJyoti SharmaLloyd J EdwardsSteven M RowePublished in: Pediatric pulmonology (2020)
Premature termination codons (PTCs) in cystic fibrosis transmembrane conductance regulator (CFTR) produce nonfunctional protein. No approved therapies exist for PTC mutations, including W1282X. We hypothesized that ivacaftor, combined with readthrough therapy, may benefit W1282X patients. Two N-of-1 clinical trials were conducted with ataluren and ivacaftor in various combinations. No meaningful clinical benefit was observed in either patient with ivacaftor alone or ataluren/ivacaftor combination. However, isolated improvements of uncertain significance were noted by a nasal potential difference (NPD) and FEV1 % with ivacaftor in Patient-1 and with ataluren/ivacaftor combination by NPD and body mass index in Patient-2. Drug regimen composed of readthrough agents and potentiators warrant further development for W1282X and other CFTR nonsense mutations.
Keyphrases
- cystic fibrosis
- pseudomonas aeruginosa
- lung function
- combination therapy
- case report
- body mass index
- clinical trial
- end stage renal disease
- randomized controlled trial
- stem cells
- chronic kidney disease
- emergency department
- newly diagnosed
- prognostic factors
- binding protein
- peritoneal dialysis
- small molecule
- physical activity
- drug induced
- bone marrow
- neuroendocrine tumors
- patient reported
- electronic health record
- amino acid
- chronic rhinosinusitis
- drug administration