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Cystic Fibrosis Therapies Rejected by NICE in Draft Guidance

Combinations of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators — ivacaftor (IVA)-tezacaftor (TEZ)-elexacaftor (ELX), tezacaftor-ivacaftor, and lumacaftor (LUM)-ivacaftor — have been judged by the NHS's spending regulator as too costly to be recommended for use in England.

The National Institute for Health and Care Excellence (NICE) decided it could not recommend the three modulator therapies, which are manufactured by Vertex, despite acknowledging that they are more beneficial than standard treatments.

Cystic fibrosis (CF) is a genetic condition affecting more than 10,900 people in the UK, according to figures from the Cystic Fibrosis Trust. The condition causes a range of challenging symptoms, and patients with CF experience a greatly reduced quality of life and shortened life expectancy, with a median age of death in 2021 of 38 years.

CF is usually caused by a mutation in the CFTR gene, called the F508del mutation. This causes the loss of phenylalanine at position 508 in the CFTR protein. NICE estimated that around 90% of those with CF had the F508del mutation.

The usual treatment aims to manage the symptoms and includes several intensive treatments and physical therapies. 

"Robust" Evidence of Benefits to Patients

In draft guidance, NICE acknowledged the substantial difficulties faced by people with CF, as well as the physically demanding and time-consuming nature of treatment. There was a "large and robust" evidence base to show that IVA-TEZ-ELX improved lung function, growth, and weight gain, and reduced the number of lung infections, more than standard treatment. "It is likely that these benefits last while people are on treatment," NICE said. It also acknowledged that TEZ-IVA and LUM-IVA also improved lung function, growth, and weight gain, and reduced the number of lung infections, more than standard treatment. "But the short- and long-term improvements are smaller than with IVA-TEZ-ELX," the regulator pointed out.

NICE agreed that CFTR modulators were clinically effective treatments that brought important benefits for people with CF with at least one F508del mutation.

In 2019, an agreement was reached between NHS England and the drug manufacturer to make LUM-IVA and TEZ-IVA available on the NHS while more evidence was collected. In 2020, the agreement was updated to include IVA-TEZ-ELX.

Patient experts on the NICE committee said that they found it "difficult and distressing" to think back to a world before CFTR modulators, having experienced their "transformative effects". 

NICE recognised that CF could substantially affect the lives of people with the condition, their families, and carers, and it acknowledged that the only alternative to CFTR modulators was standard care, which was "burdensome" and treated symptoms rather than the underlying cause. 

Not an Acceptable Use of NHS Resources

However, even when considering the condition's severity, and its effect on quality and length of life, the most likely cost-effectiveness estimates for IVA-TEZ-ELX, LUM-IVA, and TEZ-IVA were "above the range" that NICE considered an acceptable use of NHS resources, the regulator said.

NICE stressed that the latest recommendations were not intended to affect treatment with IVA-TEZ-ELX, TEZ-IVA, or LUM-IVA that was started in the NHS before the latest guidance was published, and that people having treatment outside these recommendations could continue until they and their NHS clinician considered it appropriate to stop. 

Commenting on the draft guidance, David Ramsden, CEO of the Cystic Fibrosis Trust, said that NICE's initial recommendation was "disappointing" and created "uncertainty" for those not yet on treatment.

He urged NICE, the NHS, and the drug manufacturer to "urgently work together to find a solution", so that these treatments could be made available. "We must never return to a situation where people with CF die far too young, knowing there's a treatment that could change that," he said.

The draft guidance is subject to a 4-week consultation period, after which the committee will meet to discuss the responses received.