Date: 2016-06-10
Type of information: Presentation of results at a congress
phase:
Announcement: presentation of results at the 39th European Cystic Fibrosis Society (ECFS) Conference
Company: Vertex Pharmaceuticals (USA - MA)
Product: Kalydeco® (ivacaftor)
Action
mechanism: CFTR potentiator. Ivacaftor is an oral agent that increases ion-function of activated cell-surface CFTR. The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs. Ivacaftor facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the G551D-CFTR protein. In vitro, ivacaftor increased CFTR-mediated transepithelial current (IT) in rodent cells expressing G551D-CFTR protein following addition of a cyclic adenosine monophosphate (cAMP) agonist with an EC50 of 100 ± 47 nM; however, ivacaftor did not increase IT in the absence of cAMP agonist. Ivacaftor also increased IT in human bronchial epithelial cells expressing G551D-CFTR protein following addition of a cAMP agonist with an EC50 of 236 nM. Ivacaftor increased the open probability of G551D-CFTR protein in single channel patch clamp experiments using membrane patches from rodent cells expressing G551D-CFTR protein by 10-fold versus untreated cells after addition of PKA and ATP.
Disease: cystic fibrosis
Therapeutic area: Rare diseases - Genetic diseases
Country:
Trial details:
Latest
news: * On June 10, 2016, Vertex Pharmaceuticals announced presentations of Kalydeco® (ivacaftor) data at the 39th European Cystic Fibrosis Society (ECFS) Conference , being held June 8 to 11, 2016 in Basel, Switzerland . The presentations include new real-world data from an ongoing five-year observational study evaluating long-term outcomes in cystic fibrosis patients treated with ivacaftor.
New interim data from the ongoing, five-year, post-approval observational safety study evaluating long-term outcomes in CF patients treated with ivacaftor in a real-world setting were presented this week. The following ECFS presentations are based on the third annual analysis conducted as part of this study, which uses data collected by the U.S. CF Foundation Patient Registry and the U.K. CF Registry through 2014:
"Disease progression in patients with cystic fibrosis treated with ivacaftor: analysis of real-world data from the U.K. CF Registry." ePoster ePS03.1.
"Real-world outcomes in patients with cystic fibrosis treated with ivacaftor: analysis of 2014 U.S. and U.K. registries." ePoster ePS03.2.
"Real-world outcomes in young (aged 6 to 12 years) patients with cystic fibrosis treated with ivacaftor: analysis of 2014 U.S. and U.K. CF registries data." Poster 25.
In total, these analyses included patients who had received ivacaftor for up to five years including 1,256 patients from the U.S. registry who received an average of two years of treatment and 411 patients from the U.K. registry who received an average of 1.3 years of treatment. In the U.S. registry, the annual risks of death, transplantation, hospitalization and pulmonary exacerbation were significantly lower than in the comparator cohort of matched patients who never received ivacaftor. Trends were similar in the U.K. registry, but the differences in the risk of death and transplantation were not statistically significant. No new safety concerns were identified, and the majority of the CF-related complications, such as CF-related diabetes and cultures positive for several microbial pathogens, were less common among ivacaftor-treated than untreated patients in both the U.S. and U.K. registries. Long-term follow-up data from both registries indicate clinically important outcomes in patients treated with ivacaftor in real-world settings across multiple measures of CF that are indicative of disease modification.
