On October the 24th 2019, the NHS reported a licensing agreement with Vertex Pharmaceutical’s range of Cystic Fibrosis (CF) treatments (NHS England, 2019). This comes after a series of failed financial negotiations, in which the NHS did not deem the approval of CF drugs Orkambi and Symkevi as good value for the British taxpayers (Staines, 2019). Vertex had reportedly asked for £105,000 per patient treated with Orkambi (Kmietowicz, 2019). The agreement means that within 30 days, clinicians will be able to prescribe the medicines to the 5000 CF patients who are eligible. The agreement also ensures that eligibility criteria for Kalydeco (ivacaftor) will be expanded to allow a greater number of patients to benefit from the treatment.
The financial terms of the agreement between Vertex and the NHS remain confidential, however, Vertex has agreed to a series of conditions on which the deal is based. Firstly, the company must submit its full portfolio of CF treatments to NICE. This appraisal is expected to take just under 2 years, which involves 18 months of real-world data collection. Furthermore, Vertex are required to offer the same financial terms to NHS Wales and Northern Ireland (Staines, 2019).
Orkambi will treat CF patients who have two copies of the F508del mutation in the Cystic Fibrosis Transmembrane Conductance Regulator CFTR gene. The normal function of CFTR is as a transmembrane protein which regulates the transport of Ca+ and Na+ in and out of cells (Verkman, Song and Thiagarajah, 2003). In cases where patients have both copies of an F508del mutation, CFTR proteins are incorrectly folded and do not reach the cell membrane (Sermet-Gaudelus et al., 2019). This results in a cells inability to sustain an ion gradient which normally removes water from cells through osmosis (Verkman, Song and Thiagarajah, 2003). A reduction of water in the extracellular space allows thick mucus to aggregate in epithelial cells, most notably affecting the lungs (De Lisle, 2009).
Orkambi is a combination medicine, which contains lumacaftor and ivacaftor, both of which directly target the function of CFTR. Lumacaftor functions by improving CFTR processing in the endoplasmic reticulum and subsequently increasing the proportion of CFTR proteins reaching the cell surface membrane (Van Goor et al., 2011). Ivacaftor is a CFTR potentiator, meaning that it increases the probability of defective CFTR channels opening their gating (Van Goor et al., 2009). The combination of these drugs allows for a greater number of correctly functioning CFTR proteins reaching the cell membrane. This has proven to be efficacious in improving symptoms for patients who were homozygous for F508del mutations in Phase III trials (NCT01807923 and NCT01807949). Individuals across all age groups and dose groups displayed modest improvements in FEV1% from baseline following treatment (Wainwright et al., 2015).
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Kmietowicz, Z. (2019). Cystic fibrosis drugs to be available on NHS in England within 30 days. BMJ, p.l6206.
NHS England. (2019). NHS England » NHS England concludes wide-ranging deal for cystic fibrosis drugs. [online] England.nhs.uk. Available at: https://www.england.nhs.uk/2019/10/nhs-england-concludes-wide-ranging-deal-for-cystic-fibrosis-drugs/ [Accessed 28 Oct. 2019].
Sermet-Gaudelus, I., Clancy, J., Nichols, D., Nick, J., De Boeck, K., Solomon, G., Mall, M., Bolognese, J., Bouisset, F., den Hollander, W., Paquette-Lamontagne, N., Tomkinson, N., Henig, N., Elborn, J. and Rowe, S. (2019). Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis. Journal of Cystic Fibrosis, 18(4), pp.536-542.
Staines, R. (2019). After four-year wait, patients in England finally get Vertex's cystic fibrosis drugs -. [online] Pharmaphorum.com. Available at: https://pharmaphorum.com/news/breaking-news-nhs-signs-agreement-with-vertex-covering-all-cystic-fibrosis-drugs/ [Accessed 28 Oct. 2019].
Van Goor, F., Burton, B., Hadida, S., Grootenhuis, P., Olson, E., Wine, J., Frizzell, R., Ashlock, M. and Negulescu, P. (2009). Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Journal of Cystic Fibrosis, 8, p.S17.
Van Goor, F., Hadida, S., Grootenhuis, P., Burton, B., Stack, J., Straley, K., Decker, C., Miller, M., McCartney, J., Olson, E., Wine, J., Frizzell, R., Ashlock, M. and Negulescu, P. (2011). Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proceedings of the National Academy of Sciences, 108(46), pp.18843-18848.
Verkman, A., Song, Y. and Thiagarajah, J. (2003). Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease. American Journal of Physiology-Cell Physiology, 284(1), pp.C2-C15.
Wainwright, C., Elborn, J., Ramsey, B., Marigowda, G., Huang, X., Cipolli, M., Colombo, C., Davies, J., De Boeck, K., Flume, P., Konstan, M., McColley, S., McCoy, K., McKone, E., Munck, A., Ratjen, F., Rowe, S., Waltz, D. and Boyle, M. (2015). Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. New England Journal of Medicine, 373(3), pp.220-231.
Pharmaceutical Pricing Analyst