NHS to Offer New Cystic Fibrosis Therapy Alyftrek

Hundreds of people with the most common type of cystic fibrosis could be offered a new triple therapy after the National Institute for Health and Care Excellence (NICE) recommended vanzacaftor-tezacaftor-deutivacaftor (Vnz-Tez-Diva) for routine NHS use in England.

The once-daily oral treatment, branded as Alyftrek and manufactured by Vertex, is aimed at individuals aged 6 years and over who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

When this gene is faulty, cells are unable to make normal CFTR protein to regulate intracellular levels of sodium and chloride. This leads to a buildup of the thick, sticky mucus characteristic of cystic fibrosis.

Modulators Target Underlying Cause

Vanzacaftor and tezacaftor are CFTR correctors, binding to different sites on the CFTR protein to increase its presence on cell surfaces. Deutivacaftor enhances the activity of the defective CFTR protein at the cell surface. These combined actions reduce the thickness of mucus in the lungs and digestive system.

In final draft guidance, NICE said its recommendation formed part of “an evolving treatment landscape for cystic fibrosis,” in which the advent of gene modulators is shifting care away from symptom management towards targeting the underlying cause of the disease. Helen Knight, director of medicines evaluation at NICE, said that CFTR modulators were “revolutionising” the way that cystic fibrosis is treated.

An Alternative to Kaftrio

Alyftrek was licensed in the UK in March this year and approved for use by the European Medicines Agency (EMA) in April. Alyftrek was previously designated as an orphan medicine by the EMA.

NICE’s recommendation follows a rapid assessment that compared Alyftrek with the company’s other NICE-approved triple therapy, Kaftrio (elexacaftor-tezacaftor-ivacaftor, Vertex). Evidence suggests Alyftrek is as effective as Kaftrio in improving lung function, growth, and weight gain, and in reducing the number of lung infections. Alyftrek has the additional advantage of once-daily dosing, compared with Kaftrio’s twice-daily regimen.

NICE said that Alyftrek could be offered to patients who are not eligible or able to take Kaftrio, as well as an alternative for those already taking Kaftrio.

Alyftrek is available in two dose formulations:

• Vnz 10 mg / Tez 50 mg / Diva 125 mg (84-tablet pack)
• Vnz 4 mg / Tez 20 mg / Diva 50 mg (56-tablet pack)

Both pack sizes have a list price of £16,110, excluding VAT. 

NICE’s recommendation is dependent on the company providing the drug under the terms of a confidential commercial arrangement. Clinicians are advised to prescribe the least costly suitable treatment, factoring in dosage, administration costs, and commercial terms.

David Ramsden, chief executive of the Cystic Fibrosis Trust, called the decision “a positive step in the journey to better treatments for more people with cystic fibrosis.” Similar announcements are expected to follow in Scotland, Wales, and Northern Ireland, the trust said.

NHS Expands Access Beyond NICE Scope

Following the NICE recommendation, NHS England (NHSE) announced that it had secured a commercial deal with Vertex to expand access to Alyftrek beyond the patient group considered in the regulator’s evaluation. As a result, the treatment would also be made available for children and adults with rare forms of cystic fibrosis who have not previously been eligible for modulator therapy, it said.

NHSE estimated that around 95% of people with cystic fibrosis in England are now eligible for modulator therapy.

John Stewart, NHSE’s director for specialised commissioning, described the move as “a major leap forward.”

“For those living with the rarest forms of the condition, this represents the very first time they will be able to access this new standard of care that has been so transformative for many,” he said.

Stewart added that once-daily treatment at home could reduce hospital visits and help children live more freely and independently.

Dr Sheena Meredith is an established medical writer, editor, and consultant in healthcare communications, with extensive experience writing for medical professionals and the general public. She is qualified in medicine and in law and medical ethics.