CF research update: What is the ‘vanza triple’ modulator?

Trials looking at new modulator show promising results 

Many of you will have heard of Kaftrio, but there is also another new modulator on the block, which is currently being looked at in clinical trials. Known as the ‘vanza triple’, it is a new triple combination modulator therapy 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 to take one tablet per day. 

Recent clinical trials looking at the vanza triple have shown positive results when tested in large groups of people with CF. One clinical trial looked at the effects of the vanza triple 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 the vanza triple 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. 

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

Another trial looked at the effects of the vanza triple 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. The study findings were similar to the previous studies for older children and adults. Sweat chloride levels dropped after they began taking the vanza triple. 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.

There is also another clinical trial underway looking at the vanza triple for children aged 1 year and older. This trial will look at the effects of the vanza triple in this age group over a couple of years. We will share the findings from this study when they are made available. 

You can read more about these studies on our Trials Tracker

More choice, more opportunity 

So, what happens next? Following these positive results, the trial sponsor (the company who runs these trials) Vertex has announced they will be submitting a license application for this new therapy to be a treatment option for people with CF aged 6 and over in the US and Europe including the UK. 

For people with CF to have access to this treatment, the vanza triple will need to be approved by the Medicine and Healthcare products Regulatory Agency (MHRA), who regulate medicines in the UK. 

It will also need to be assessed by the National Institute for Health and Care Excellence (NICE), which assesses the clinical and cost-effectiveness of medicines in England. NICE make recommendations whether they should be available on the NHS. We expect this appraisal process to be different to how Kaftrio, Orkambi and Symkevi were assessed, and this should take place in 2025. Wales and Northern Ireland will adopt NICE’s recommendations, and a separate assessment will happen in Scotland. 

This is a really exciting development in CF modulator research. Finding more effective modulator treatments is essential to continue reducing the burden of CF treatment for people with CF. 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 the opportunities to access treatments that work best for them. 

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 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.

Thank you! 

These exciting developments are only made possible by people with CF taking part in clinical trials. A big thank you to everyone who has been involved. If you’d like to find out more about clinical trials and how you can sign up, visit our CF Trials Tracker. 

You can read more about the vanza triple in our Q&A