Can single-medicine treatment with CFTR modulators (medicines that correct the faulty protein in cystic fibrosis) help people who have specific genetic variants of cystic fibrosis (most commonly F508del)?

Key messages

• All the studies only included people with two copies of the most common cystic fibrosis-causing gene variant (F508del).

• Most studies were entirely or partly funded by medicine companies. No studies reported any deaths. None of the single medicines we looked at were clearly better than placebo (dummy treatment) for improving quality of life or lung function, and there was no evidence of the medicines causing more harm than placebo. However, we are unsure about these results.

• The evidence for using a single CFTR modulator is weak, and future research is likely to focus on combination therapies.

What is cystic fibrosis and how can it be treated?

Cystic fibrosis is a serious inherited illness that shortens life. It damages many organs in the body, particularly the lungs, pancreas, and liver. In the lungs, it causes a build-up of thick, sticky mucus that leads to repeated infections and progressive damage. Most people with cystic fibrosis experience breathing difficulties, poor nutrition, and a reduced quality of life.

Cystic fibrosis is caused by a fault in a gene that makes a protein called CFTR. CFTR regulates the movement of salt and water across cell surfaces, keeping the mucus thin and slippery. The most common CFTR gene variant (found in over 80% of people with cystic fibrosis) is F508del, which is a class II variant. People with two copies of F508del usually have more severe disease than people with one copy. In people with class II variants, the CFTR protein is degraded and cannot move properly through the cell. Laboratory experiments suggest that if the protein reaches the cell wall, it may be able to function, restore salt movement, and correct the chronic problems people with cystic fibrosis experience. CFTR modulators are medicines that help the faulty CFTR protein reach the cell wall.

What did we want to find out?

We wanted to know if CFTR modulator monotherapy (single-medicine treatment) can help people of any age with cystic fibrosis who have a class II variant. Specifically, we wanted to know if these medicines can improve survival, quality of life, lung function, and time to the first worsening of lung symptoms. We also wanted to know if this treatment is associated with any unwanted effects.

What did we do?

We searched for studies that investigated the effects of any single CFTR modulator compared with placebo (dummy treatment) or any other single CFTR modulator in people with cystic fibrosis who had at least one copy of a class II variant. We compared and summarised the results of the studies and rated our confidence in the evidence based on factors such as study methods and sizes.

What did we find?

We found 10 studies (with 424 participants, all of whom had two copies of F508del) assessing eight different medicines given as monotherapy. Nine studies included only adults, and one study included people from age 14 years. All the studies were small (including between 18 and 89 participants) and lasted between one day and 29 days. They took place in North America (mainly the USA), Europe, and Australia. Our main findings are for two of the eight medicines, lumacaftor and cavosonstat, which have gone on to be evaluated in larger populations.

Main findings

No studies reported any deaths or meaningful improvements in quality of life. We did not find enough evidence to show any effect of CFTR modulators on lung function. The studies reported a wide range of unwanted effects, but each occurred in only a few participants per study. We did not find enough evidence to support using CFTR modulator monotherapy in people with cystic fibrosis who have two copies of F508del.

What are the limitations of the evidence?

We are not confident in the evidence, for the following reasons.

• The studies were small.

• Most results are based on evidence from a single study.

• The evidence is not applicable to children.

• Not all studies provided enough data for us to analyse the results.

• The evidence related to unwanted effects of treatment was based on very few events.

How up-to-date is this evidence?

This review updates our earlier review of single- and multiple-medicine therapy. The evidence is current to 27 June 2025.