Ivacaftor, a novel oral agent that potentiates a membrane channel blocked in patients aged six years and older with cystic fibrosis caused by the G551D mutation, significantly improves lung function and reduces pulmonary exacerbations, according to phase 3 data reported at the European Respiratory Society's Annual Congress 2012, Vienna, on Monday (3 September 2012). Open label follow-up showed the improved lung function and good tolerability was maintained with continued treatment.

The STRIVE study randomised 161 patients aged 12 and over with cystic fibrosis and at least one copy of the G551D mutation in the CFTR gene to ivacaftor (150mg every 12 hours) or placebo. Results showed a mean absolute improvement of 10.6% in predicted FEV1 after 24 weeks' treatment with ivacaftor compared to placebo (p<0.0001), sustained at 10.5% at 48 weeks.

The ENVISION study, which included 52 children aged 6-11 years, showed similar absolute improvement of 12.5% in predicted FEV1 with ivacaftor at 24 weeks compared to placebo (p<0.0001), with a 10.0% improvement maintained at 48 weeks.

STRIVE showed a significant reduction in pulmonary exacerbations and clinically significant improvement in the respiratory domain of patients' quality of life with ivacaftor. Both studies showed an increase in body weight (mean increases of 2.7kg at 48 weeks in STRIVE and 2.8kg in ENVISION).

"Ivacaftor is the first medicine to treat the underlying cause of cystic fibrosis in people with the G551D mutation, a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene," said Stuart Elborn, Professor of Respiratory Medicine at Queen's University, Belfast, Northern Ireland and a principal investigator. "These data showing the consistent and sustained benefit of this medicine confirm that ivacaftor has the potential to make a significant difference to the lives of children, adolescents and adults with this form of CF."

He added: "The data don't capture the full benefit for patients. It's been very noticeable in the patients I look after that they are able to do things they previously couldn't after starting treatment with ivacaftor. They feel better and more able to plan for the future."

Fewer patients in the ivacaftor treatment groups discontinued treatment due to adverse events compared to placebo in both trials. Most adverse events associated with ivacaftor were mild to moderate, with some of the commonest including headache, upper respiratory tract infection, rash, diarrhea and abdominal pain.

Data reported from the follow-up PERSIST study showed that improvements in lung function with ivacaftor were sustained for patients continuing treatment from the STRIVE and ENVISION trials for up to 96 weeks. Those switched from placebo to open-label ivacaftor showed similar improvements in FEV1 to those seen in the patients starting on the drug during the placebo-controlled trials.

Reporting the findings, Dr Edward McKone, Consultant Respiratory Physician at St Vincent's University Hospital, Dublin, Ireland, said:

"We saw three main things: the efficacy with ivacaftor is sustained for up to 96 weeks; reproducible benefits for the placebo groups in the original trials; and, most importantly, the overall safety profile showed no new safety concerns."

Written by Susan Mayor PhD (Freelance Medical Journalist, London, UK)