Correction of the 508del-CFTR protein processing defect in vitro by the investigational drug VX-809.

Negulescu and colleagues published a "proof of concept" experiment showing that the novel molecule called VX-809 could correct in vitro the very common and critical 508del-CFTR mutation identified by Collins. (See GM 13570). When undergoing trials in humans this drug, manufactured under the trade name Lumacaftor by Vertex Pharmaceuticals, failed to perform as well as expected. Vertex then developed other combination drugs that enhanced the in vivo effect of VX-809, leading to the duel combination drug they called Orkambi. These drugs led to long term remissions, greatly improved quality of life, and a longer life span for CF patients. Regrettably, in 2018 the cost of Orkambi for a single CF patient was around $275,000 per year. Order of authorship in the original publication: Van Goor, Hadida, Grottenhuis, et al, Negulescu. Digital text from pnas.org at this link.

(Thanks to Juan Weiss for this reference and its interpretation.)