Alyftrek

Alyftrek, previously known as the vanza triple, is a new triple combination modulator therapy being looked at in clinical trials. It is made up of tezacaftor, one of the modulators used in Kaftrio, as well as two new modulators called vanzacaftor and deutivacaftor. 

This combination has the potential to give longer lasting benefit, meaning people need only take one dose per day.

Clinical trials have been looking at whether Alyftrek is as effective as Kaftrio for people with CF with certain gene variants.

A couple of recent clinical trials have looked at Alyftrek in large groups of people with CF. 

One clinical trial looked at the effects of Alyftrek in around 400 people with CF ages 12 and older who had one F508del CFTR gene variant and one minimal function CFTR gene variant. 

A second trial looked at Alyftrek in a larger group of more than 550 people aged 12 and older with at least one CFTR gene variant that is responsive to modulators like Kaftrio. 

The trials followed participants over the course of a year. All participants began by taking Kaftrio for four weeks. They were then randomly assigned to one of two groups. The first group received Alyftrek and the other continued on Kaftrio.

We’ve published summaries of these results on the Trials Tracker listings as part of our work to make clinical trial results more accessible.

Both studies showed Alyftrek was ‘at least’ as good as Kaftrio in improving and maintaining lung function in people with CF. Alyftrek had better results in reducing sweat chloride levels. A higher number of people taking Alyftrek had sweat chloride levels below the level to be diagnosed as having CF or being a carrier.

Those with 1 or more F508del mutations in the CFTR gene in people 6 years and over. Alyftrek is also potentially an option for approximately 150 people with CF in the US with one of 31 mutations who are now eligible for a CFTR modulator for the first time.  

We hope that future clinical trials will help us understand who else could benefit from this therapy.

Following these clinical trials looking at people aged 12 and older, another trial looked at the effects of Alyftrek in children aged 6 to 11. Seventy-eight children with at least one CFTR gene variant that is responsive to modulator therapies like Kaftrio took part. They were asked to take Kaftrio for four weeks followed by Alyftrek for up to 24 weeks. 

The study findings were similar to the previous studies for older children and adults. Sweat chloride levels dropped after they began taking Alyftrek. At 24 weeks, 95% of children in the study had sweat chloride levels that were below the level to be diagnosed as having CF and a majority achieved sweat chloride levels below the level to be diagnosed as a carrier.

Another clinical trial is now underway looking at the vanza triple for children aged 1 year and older. This trial will look at the effects of Alyftrek in this age group over a couple of years. We will share the findings from this study when they are made available. This study will help to understand if Alyftrek can be recommended as a treatment for this age group. 

If Alyftrek is approved in the UK, the Cystic Fibrosis Medical Association (CFMA) has advised that the decision to switch from Kaftrio to Alyftrek will be made jointly between the person with CF and their CF team, after consideration of the potential risks and benefits.

Following these positive trial results, the U.S. Food and Drug Administration (FDA) has now approved the vanza triple (brand name Alyftrek) for people with cystic fibrosis ages 6 and older who have a mutation that is eligible for Kaftrio or one of 31 rare mutations that had not been approved previously for a modulator.  

Wales and Northern Ireland will adopt NICE’s recommendations, and a separate assessment will happen in Scotland.

In March 2025, the drug was approved for use by MHRA, the UK agency responsible for ensuring medicines are safe. Both the MHRA and NICE must approve the drug for use for it to become available on the NHS.

The NICE appraisal is separate to the appraisal of Kaftrio, Symkevi and Orkambi which concluded in June 2024, and does not affect the permanent access agreement with the NHS that is in the place for those medicines. You can read more about this here. 

We expect NICE to publish their guidance in summer 2025, so it is possible – subject to approvals – it could be available in autumn 2025.  

Wales and Northern Ireland adopt NICE’s recommendations. In Scotland, the Scottish Medicines Consortium (SMC) is assessing Alyftrek and we expect the timelines will be similar to NICE’s.   

While Kaftrio has had huge benefits for many people with CF, not everyone can tolerate or benefit from these modulators in the same way. We need more choices so people with CF have more opportunity to access treatments that work best for them.

A new trial currently looking for participants is aiming to learn more about the effects of Kaftrio in children aged 12 months to younger than 24 months. Kaftrio has been approved for children aged 2 years and older, but has not yet been approved for this age group.

Research is continuing to look at improving modulator options for everyone with CF. For example, the ongoing HIT-CF and CHOICES study is looking at a new triple combination modulator therapy in people with rare gene variants who are not eligible for Kaftrio. There are two parts to this study. Recruitment is currently open for the second part of the study, however you must have taken part in the first part of the study to take part. 

We know that modulators don’t work for everyone, and we won’t stop until everyone with CF can access the treatments and medicines they need. We will continue to invest money in life-saving research to find treatments for all. 

We are funding a number of lab-based research studies that could benefit people with rare mutations who currently are not eligible for modulators. Early phase genetic therapy clinical trials are also now recruiting a few people with CF in the UK. They’re in the very early stages, but they hold a lot of promise for the future. You can take a look at genetic therapy clinical trials for CF on our Trials Tracker.

We’re also working actively to improve the day-to-day symptoms of everyone with CF. This includes diagnosing and developing better treatments for infections that are becoming resistant to current medicines. We’re doing this by funding research directly and supporting researchers in universities and in the pharmaceutical industry through the CF AMR Syndicate initiative run in partnership with Medicines Discovery Catapult and LifeArc.

The CFMA welcomes the recent MHRA approval for the new triple CFTR modulator therapy, Alyftrek. This new medicine may offer an important alternative for some people with CF who are already treated with Kaftrio, with data from the clinical trials showing that it is comparable to Kaftrio at improving lung function. Alyftrek may also be an option for a small number of people who are not eligible for current therapies or have not been able to tolerate them, but current clinical trial data hasn’t revealed the specifics of this. While improvements to therapies is good news, ongoing challenges exist for people with the condition and CF clinical teams will continue to work to achieve excellent health outcomes and quality of life for all. CF remains a condition without a cure and we hope that new therapies will become available for people with CF in the future, particularly for those who do not respond to existing therapies.