NHS England And Vertex Strike “Lightening Quick” CF Kaftrio/Trikafta Deal

An agreement between Vertex and NHS England secures rapid access to Kaftrio, the company’s triple therapy for cystic fibrosis, including for patients with rare mutations not covered by the soon-to-be-granted European marketing authorization. The final price will depend on an assessment by health technology appraisal body NICE.

Vertex and NHS England Have Extended Their CF Treatment Deal

Vertex Pharmaceuticals and National Health Service England have expanded the portfolio style cystic fibrosis treatment agreement that was struck in October 2019 ending years of acrimony to include the company’s new triple therapy, Kaftrio (ivacaftor/tezacaftor/elexacaftor).

The deal will give patients in England access to Kaftrio as soon as it receives official EU marketing authorization, while further data is gathered to inform a health technology appraisal. Kaftrio – known as Trikafta in the US, where it was approved in October 2019 – should be approved in the coming months. 

Thanks to the expanded agreement, “nine out of 10 patients with cystic fibrosis – more than 7,000 people – will now benefit from a therapy which tackles the underlying causes of the disease, by helping the lungs work effectively,” according to NHS England.

Vertex has agreed to offer “equivalent terms” in the other nations of the UK - Scotland, Wales and Northern Ireland.

One industry association described the deal as “lighting quick”.

NHS England and Vertex announced the news just days after the European Medicines Agency’s Committee for Medicinal Products for Human Use adopted a positive marketing recommendation for Kaftrio in combination with Kalydeco (ivacaftor)  for treating CF patients aged 12 and older with F508del mutations or one F508del mutation and one minimal function mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. (Also see "Vertex's Triple CF Combo Gets EU Approval Nod; Rejection For Daiichi Sankyo" - Pink Sheet, 26 Jun, 2020.) The European Commission should issue the official marketing authorization within 67 days of the CHMP opinion being adopted. Centralized marketing authorizations are valid in all EU member states as well as in the UK and the European Economic Area countries of Iceland, Liechtenstein and Norway.

The deal struck in 2019, covering access to Orkambi (lumacaftor/ivacaftor) and Symkevi (tezacaftor/ivacaftor), came after years of acrimonious wrangling. There was angry campaigning from patient groups as well as public petitions, parliamentary debates, a parliamentary inquiry, and a public hearing on the issue.

"We look forward to working with the company and the NHS on continued data collection for all three products involved in advance of our formal appraisal process.” – NICE chief executive Gill Leng.

That initial agreement provided access to Orkambi and Symkevi in all current and future indications and expanded access to Kalydeco. (Also see "At Last: Vertex Strikes CF Deal In England" - Pink Sheet, 24 Oct, 2019.) It was also agreed that real world evidence would be gathered to better understand the effects of Orkambi and Symkevi and to inform assessments by NICE, the health technology assessment body for England and Wales. In addition, Vertex committed to submitting its triple therapy to a NICE assessment.

Under the expanded four-year agreement announced on 30 June, Kaftrio will indeed be subject to a NICE assessment after a period of real world data collection on all three medicines. Prices will be adjusted “as necessary” following a full appraisal, “to ensure that taxpayers continue to get a good deal,” according to NHS England.

NICE chief executive Gill Leng said of the agreement: “[It] will ensure people with cystic fibrosis can access this important new treatment while further data on its benefits are collected. We look forward to working with the company and the NHS on continued data collection for all three products involved in advance of our formal appraisal process.”

NICE Processes

NICE refused to recommend Orkambi back in 2016, saying that its benefits did not outweigh its costs. The subsequent failure to reach an access arrangement for the treatment was in large part down to the fact that Vertex believed the NICE standard review process to be inappropriate for a rare disease drug like Orkambi. It claimed that science was “outpacing” the NICE system. (Also see "Vertex Commits To Novel Reimbursement Plan For Orkambi In UK, Despite Setback " - Pink Sheet, 22 Mar, 2018.) The company subsequently declined to engage in a NICE appraisal of Symkevi.  Meanwhile, Vertex was accused of intransigence. At a public hearing, then NICE chief executive Andrew Dillon said that in 20 years at the institute he had never seen a company demonstrate such little “flexibility in its expectations.”

Following the latest agreements, Vertex told the Pink Sheet that it was committed to submitting to NICE within the agreed timetable “as this is the formal route to access for medicines in England.” It said it was “confident that the value of the triple combination seen by NHS England will be there going forward.”

Despite this commitment, Vertex clearly still has doubts about current NICE processes and wants to see change. “We welcome NICE’s ongoing review into its methods and are playing an active role alongside industry and other stakeholder groups.  We hope that the process will lead to real reform in particular for rare diseases,” it said.

Real world data gathering in partnership with the Cystic Fibrosis Trust, the UK CF Trust Registry and NICE began in February for Orkambi and Symkevi, Vertex said. It added that Covid 19 had not had a significant impact on data collection.

Comprehensive And Quick

The expanded agreement is among "the most comprehensive access arrangements of any country in Europe,” said John Stewart, National Director, Specialised Commissioning NHS England.

In a letter to Cystic Fybrosis Trust chief executive David Ramsden, Stewart pointed to terms of the deal that mean around 300 CF patients with rare mutations not be covered by the European approval will be able to access Kaftrio and other treatments in the portfolio. These mutations are included in US approvals granted by the Food and Drug Administration. The deal also includes all future license extensions for the triple therapy.

"[This is one of the] most comprehensive access arrangements of any country in Europe." – John Stewart, National Director, Specialised Commissioning NHS England.

Steve Bates, chief executive of the UK BioIndustry Association, described the deal as “lightening quick”. “The speed of this deal will not only improve the health outcomes of many people with cystic fibrosis, but also sends a clear message to the global life sciences industry that the UK is a great place to develop, trial, and launch innovative medicines," Bates said.

Meanwhile, Vertex CEO and president Reshma Kewalramani said in a statement that “Vertex and NHS England have been able to work quickly, collaboratively and flexibly to expand the existing reimbursement agreement to include the triple combination therapy in advance of the medicine being licensed.” Kewalramani said this would ensure that patients in England would be the “among the first in Europe to benefit from access to this innovative medicine upon approval.”

Quick access to the triple therapy could be in place elsewhere soon in countries that have agreed to similar portfolio style deals. Vertex said that it had agreed a deal in April with the authorities in Switzerland that secured reimbursement for Orkambi and Symkevi and allowed “the possibility of rapid patient access to the triple combination regimen once it’s approved [there]”.

A portfolio style arrangement is also in place in Denmark. Signed in October 2018, the agreement included “current and future CFTR modulator medicines and means eligible Danish cystic fibrosis patients will have access to all current medicines as well as future medicines after regulatory approval,” according to a statement released at the time. (Also see "Vertex Extends Portfolio Pricing and Reimbursement Approach To Denmark" - Pink Sheet, 10 Oct, 2018.)

A 2018 agreement in Sweden also provided a “framework for the assessment and access of our future CF medicines.” The blueprint for these agreements was the deal struck in Ireland in 2017. (Also see "Vertex Strikes Novel Reimbursement Deal For Cystic Fibrosis Drugs in Ireland" - Pink Sheet, 8 Jun, 2017.)

Vertex said it was “prepared to work creatively and flexibly with national health authorities and governments to secure access once the triple combination regimen is licensed, and in many cases are already doing so in advance of regulatory approval.”

The agreement is one of a growing number of commercial access deals agreed between companies and NHS England after the body established a new commercial medicines function.