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vertex 770 and r347p

Question
Dear team,
my daugther FC has got mutation r347p (class iv).
I red that vertex 770 could work on r117h (class iv too).
Is the defect of conductance caused by r347p similat to the defect caused by r117h?
Is it probable that vertex 770 can work also for r347p?
In case it works for r117h, will it be possible to have vertex off label for my daugther and, in general, for patients with class iv mutations other than r117h?
Thank you!
annalisa
(afalabella@kstudioassociato.it)
Answer
Dear Questioner
Thank you for your question.
KALYDECO (ivacaftor, VX-770) is a medicine in development for the treatment of people with cystic fibrosis and the G551D CFTR mutation by a pharmaceutical company called Vertex.
In CF, the defect in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene, causes defective production of the CFTR protein; ranging from no protein production at all, to producing protein that works only some of the time (mutations ranging I-VI). In class IV mutations; CFTR protein is made, and reaches the cell surface; however it does not work properly when is gets there. This means that the protein cannot function properly as a channel to transport ions which control the hydration of the lungs and other organs as it should. This happens with both R117H and R347P mutations.
Known as a CFTR potentiator, KALYDECO is an oral medicine that aims to help CFTR protein function more normally once it reaches the cell surface, to help hydrate and clear mucus from the airways. The drug has recently received FDA approval and it is currently being considered via accelerated assessment by the European Medicines Agency (EMA) for approval for use in patients with a G551D mutation only, following rigorous clinical trials in this group of patients demonstrating the drug to be safe and effective.
Future Vertex programmes to study the effects of KALYDECO in people with the R117H mutation are currently being set up (as this is the most common mutation in the class IV group) and there are plans to extend this research into other gating mutations, possibly to include the R347P mutation (which account for a smaller % of class IV mutations)
Before these studies have been carried out, the effects of the drug in people with this class of mutation are unknown and the drug is not indicated for use in this group until a clinical trial has been completed demonstrating the drug to be safe and effective.

Regards
Katherine Treacy Research Physiotherapist, Belfast
Prof stuart Elborn Consultant Physician, Belfast


References
Elborn JS. Fixing cystic fibrosis CFTR with correctors and potentiators. Off to a good start. Thorax 2012 January 01;67(1):4-5.
Vertex Pharmaceuticals Incorporated Press release January 8, 2012 Vertex Announces Key 2012 Business Objectives as Company Prepares for Planned Global Launch of KALYDECO in Cystic Fibrosis
Vertex Pharmaceuticals Incorporated Press release January 31, 2012 FDA Approves KALYDECOâ„¢ (ivacaftor), the First Medicine to Treat the Underlying Cause of Cystic Fibrosis

21.02.2012
The answer is edited by: Prof Stuart Elborn