New cystic fibrosis triple from Vertex backed for NHS use

Vertex Pharma has added another exon-skipping therapy for cystic fibrosis to its portfolio of drugs that can be prescribed by the NHS in England and Wales for patients with the genetic disorder.

Reimbursement authority NICE has backed routine NHS use of Vertex's once-daily triple therapy Alyftrek (deutivacaftor/tezacaftor/vanzacaftor) for all eligible individuals with cystic fibrosis aged six and over who have at least one F508del mutation or another responsive mutation in the CFTR gene, which is faulty in the disease.

Vertex's strategy in cystic fibrosis has always been to progressively improve its therapies, based on compounds that modulate the activity of CFTR, to extend the range of mutations covered by the drugs and provide greater efficacy, and Alyftrek fits squarely into that mould.

It is an alternative to older twice-daily triplet Kaftrio (elexacaftor/tezacaftor/ivacaftor), but can be used in a wider population of cystic fibrosis patients, with NICE estimating it will be an option for 89% of all cystic fibrosis patients in England.

In trials, Alyftrek matched its predecessor at improving lung function scores, but also improved on its ability to lower chloride in sweat, a biomarker for disease severity.

In a statement, NICE said: "Evidence suggests Alyftrek is as effective as Kaftrio, with similar costs, following a commercial agreement between NHS England and Vertex."

Alyftrek was approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in March based on the results of the SKYLINE 102 and SKYLINE 103 trials.

The data revealed that the new triple therapy was significantly more effective at achieving a sweat chloride level below 60 mmol/L, which is the threshold for a cystic fibrosis diagnosis, with 86% of patients on the new drug hitting that target at week 25 versus 77% of the Kaftrio group.

NICE's decision has been welcomed by Prof Kevin Southern, chair of the UK Cystic Fibrosis Medical Association (CFMA), who said Alyftrek "may offer an important alternative for some people with CF who are already treated with Kaftrio, or be an option for a small number of people who are not eligible for current therapies or have not been able to tolerate them."

Kaftrio made more than $10 billion in global sales last year, accounting for more than 90% of Vertex's revenues. So far, the company has not divulged sales of Alyftrek, which was approved in the US, its first market, last December, and also got the green light in the EU in April.

In the EU, eligible patients in Ireland, Denmark, and Germany will be the first ones to access the new drug after the conclusion of reimbursement negotiations.

Ludovic Fenaux, senior vice president of Vertex International, said the company is "pleased to have reached this agreement with NHS England that recognises the value that this new medicine brings to CF patients, their families, and society."

Vertex is currently enrolling and dosing subjects in a phase 3 study of Alyftrek in children aged two to five years with cystic fibrosis in the hope of further broadening the drug's label.