Vertex Pharmaceuticals scientists presented positive results from clinical studies evaluating Kalydeco (ivacaftor) and Orkambi (lumacaftor/ivacaftor) at the 39th European Cystic Fibrosis Society (ECFS) Conference June 8-11 in Basel, Switzerland.
The presentations included real-world data from an ongoing observational study with cystic fibrosis (CF) patients treated with ivacaftor, and a Phase 3 safety study for lumacaftor/ivacaftor in children between 6-11 years old with cystic fibrosis.
In the first study, three posters analyzed cystic fibrosis patients’ outcomes after ivacaftor treatment for up to five years — including patients from both the U.S. CF Foundation Patient Registry and the U.K. CF Registry. In total, researchers analyzed 1,256 patients from the U.S. registry (with an treatment duration of two years), and 411 patients from the U.K. registry (with an average treatment duration of 1.3 years).
Researchers observed in the U.S. patient cohort treated with ivacaftor significant lower registries for annual risks of death, transplantation, hospitalization, and pulmonary exacerbation, when compared to cystic fibrosis patients who were never treated with ivacaftor. The U.K. cohort exhibited the same trend, although no significant changes were detected for the risk of death and transplantation, compared to untreated controls.
Scientists detected no new safety concerns, and the frequency of reported CF-related complications (CF-related diabetes and cultures positive for several microbial pathogens) showed lower frequencies in the treated cohorts (both in the U.S. and U.K., relative to untreated controls).
The Phase 3 safety study assessing lumacaftor/ivacaftor enrolled 58 children ages 6-11 with cystic fibrosis, carrying two copies of the F508del mutation. Children received a combination of lumacaftor (200 mg) and ivacaftor (250 mg) twice daily over 24 weeks.
Treatment was well-tolerated, and the most common adverse events included cough, headache, and infective pulmonary exacerbation, nasal congestion, abdominal pain, increased sputum, and elevated liver enzymes.
At 24 weeks, cystic fibrosis patients showed improvements in several secondary endpoints, including decreased concentration of sweat chloride (-24.8 mmol/L), weight gain (2.6 kg), improved CFQ-R respiratory domain score by 5.4 points, improvement in lung function (FEV1 of 2.5 percentage points), and improvement in the exploratory endpoint of lung clearance index.
In the U.S., the FDA granted Vertex a Priority Review of a supplemental New Drug Application (sNDA). The company is seeking approval of Orkambi as a treatment for children ages 6-11 with CF who carry two copies of the F508del mutation.
In Europe, Vertex is waiting for the results of an ongoing study evaluating Orkambi in 200 children, with the primary endpoint being the absolute change in lung clearance index. Once the study is complete, Vertex plans to file for a Marketing Authorization Application (MAA) variation in the European Union in the first half of 2017.
“Our scientists have been working for many years to change the way CF is treated by developing medicines that address the underlying cause of the disease,” Jeffrey Chodakewitz, M.D., executive vice president and chief medical officer at Vertex, said in a press release.
“As more data for Kalydeco and Orkambi become available, we are increasingly confident that treating the underlying cause of the disease slows its progression and results in a range of benefits across multiple measures of CF. We’re committed to continuing our efforts to help the two out of three people with CF who don’t currently have a medicine that treats the underlying cause of their disease,” he added.