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Rapid response to:


MPs call for fresh talks to end deadlock over cystic fibrosis drug

BMJ 2018; 360 doi: (Published 21 March 2018) Cite this as: BMJ 2018;360:k1337

Rapid Response:

Re: MPs call for fresh talks to end deadlock over cystic fibrosis drug

Dear Editorial Team;
Over the last 40 years, incremental improvements in the care for people with cystic fibrosis (CF) has resulted in improved survival for individuals with this devastating genetic disease.1 However, in the current decade treatment for CF has made a step change to therapies which correct the cellular defect in chloride transport and could potentially have a transformative impact on morbidity and mortality.1,2 In the UK, ivacaftor has been reimbursed for around 5% of patients with specific gene mutations since 2013. A recent study of UK and US patients with the G551D mutation (the largest group in whom protein function is corrected by ivacaftor) showed improved survival and less requirement for lung transplantation compared to matched controls3.
A combination of ivacaftor and lumacaftor (Orkambi)4 was approved by the European Medicines Agency in 20155 for people with CF who are homozygous for the F508del gene mutation (approximately 50% of people with CF in the UK). This therapy has undergone health technology assessment through NICE and was considered by the Scottish Medicinesby Consortium (SMC). It was found to have efficacy, but the cost was considered too high for the benefit derived by patients.6,7 The main beneficial effect is to reduce pulmonary exacerbations and reduce hospitalisations.4 Protracted discussions between NICE, NHS England and the SMC with the pharmaceutical company which manufactures these drugs, Vertex, have failed to reach resolution and most people with CF in the UK do not have access to this therapy. This was highlighted in March through parliamentary discussion and debate8 and on 9th November 2018, the Chair of the Health and Social Care Committee Sarah Wollaston asked for full disclosure of all correspondence between Vertex, NICE and NHS England relating to the pricing of Orkambi.9
The position in the UK contrasts with most other countries where cystic fibrosis is prevalent. People with CF in the United States, most of Europe and Australia have access to this combination therapy. Understandably, this has led to significant frustration and anger for children and adults with CF and their families in the UK. Concern about access to effective treatment is further heightened by the development of new triple combinations of CFTR modulators which are currently being evaluated in phase III clinical trials (including participants from the UK). Phase II clinical trials suggest these combination therapies will be very effective in people with CF and will benefit around 90% of patients.10 Discussions between NHSE and Vertex have involved a portfolio deal which includes these potentially transformative drugs for the majority of people with CF with the most common mutation, F508del.

As representatives of the UK clinical community, we believe that access to current and future approved therapies for people with CF is critically important. Patients who will benefit from these treatments are being denied an effective therapy which has been approved by the appropriate regulatory body and has market authorisation. We fully support the health technology assessment undertaken by NICE and agree that the combination of ivacaftor and lumacaftor has efficacy. It is however now intolerable for people with CF and their care teams that after 3 years, a fair price has not been negotiated between Vertex and our commissioning bodies in the NHS. It is inequitable that such treatments are available to most of the world’s CF community, but not in the UK. This limits our options as paediatric and adult physicians to provide optimal treatment for people with CF in this country.
Clinicians in the UK want to use these therapies and people with CF wish to be treated with these drugs. It is therefore incumbent that Vertex work with NICE and UK commissioners to strike a fair deal based on the robust health technology assessment undertaken, to enable us to deliver the best care possible for people with CF in the UK.

Caroline Elston
J Stuart Elborn*
Charles Haworth
Gary Connett

On behalf of the UK Cystic Fibrosis Medical Association.

J Stuart Elborn
Imperial College London and Royal Brompton Hospital
Fulham Road, London, SW3 6HP


1: Elborn JS. Cystic fibrosis. Lancet. 2016 Nov 19;388(10059):2519-2531. doi:
10.1016/S0140-6736(16)00576-6. Epub 2016 Apr 29. Review. PubMed PMID: 27140670.

2: Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, Griese M,
McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe
SM, Dong Q, Rodriguez S, Yen K, Ordoñez C, Elborn JS; VX08-770-102 Study Group. A
CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl
J Med. 2011 Nov 3;365(18):1663-72. doi: 10.1056/NEJMoa1105185. PubMed PMID:
22047557; PubMed Central PMCID: PMC3230303

3: Bessonova L, Volkova N, Higgins M, Bengtsson L, Tian S, Simard C, Konstan MW,
Sawicki GS, Sewall A, Nyangoma S, Elbert A, Marshall BC, Bilton D. Data from the
US and UK cystic fibrosis registries support disease modification by CFTR
modulation with ivacaftor. Thorax. 2018 Aug;73(8):731-740. doi:
10.1136/thoraxjnl-2017-210394. Epub 2018 May 10. PubMed PMID: 29748252..

4: Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo
C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF,
Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT
Study Group. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for
Phe508del CFTR. N Engl J Med. 2015 Jul 16;373(3):220-31. doi:
10.1056/NEJMoa1409547. Epub 2015 May 17. PubMed PMID: 25981758; PubMed Central
PMCID: PMC4764353.




8: BMJ 2018;360:k1337


10: Holguin F. N Engl J Med. 2018 Oct 25;379(17):1671-1672. doi: 10.1056/NEJMe1811996. Epub 2018

Competing interests: Conflicts of interest: CE has received speaker fees from Vertex. JSE has participated in advisory boards with Vertex, Galapagos and Proteostasis. He has contributed as a chief and principal investigator in clinical trials of drugs developed by Vertex. All monies for clinical trials are paid to the Royal Brompton Hospital. The Royal Brompton Hospital is in receipt of a NHS England/ABPI innovation grant supported by Vertex which he co-leads. CSH has received consultancy fees, speaker fees and research grants from Vertex. He has contributed as a site principal investigator in clinical trials of drugs developed by Vertex and Galapagos. All monies for clinical trial work go to Royal Papworth Hospital. GC has participated in advisory boards for Mylan and Novartis. He has contributed as a principal investigator in clinical trials developed by Vertex and Gilead. All monies for clinical trials also go to University Hospital Southampton. UK CF Medical Association (UKCFMA) This is an Association of medical doctors in the UK who deliver clinical care to children and adults with cystic fibrosis. The Association formed in 2018. The purpose of the Association is to advocate for optimum care of people with cystic fibrosis in the UK. The Association receives support from the UK CF Trust to undertake it’s activities. It receives no sponsorship from the pharmaceutical industry. This letter was circulated to all members of the UKCFMA and was is endorsed by 98 Consultants from UK CF centres. Three did not support the content. Some members of UKCFMA have contributed to advisory boards and /or been a PI on clinical trials sponsored by Vertex.

10 November 2018
J. Stuart Elborn
Clinical academic
Caroline Elston, Charles Haworth, Gary Connett
Royal Brompton Hospital /Imperial college london
Royal Brompton Hospital, Sydney St, London SW16NP