Final data from PROGRESS study of Orkambi (lumacaftor + ivacaftor) for cystic fibrosis patients with F508del mutation- Vertex

Presentations given at the 30th Annual North American Cystic Fibrosis Conference (NACFC) include final data from the PROGRESS 96-week extension study of the pivotal 24-week Phase III studies of Orkambi (lumacaftor + ivacaftor) in people aged 12 and older with two copies of the F508del mutation (TRAFFIC and TRANSPORT). Other highlights include an analysis of real-world outcomes in patients treated with Kalydeco using data from the United States Cystic Fibrosis Foundation Patient Registry (US CFFPR) and United Kingdom Cystic Fibrosis Registry (UK CFR).

Abstract #180, Workshop 07: Clinical Advances in CF Research. An analysis of 96-week data from the PROGRESS extension study of the pivotal Phase III TRAFFIC and TRANSPORT studies of lumacaftor/ivacaftor in people ages 12 and older with two copies of the F508del mutation showed that lumacaftor/ivacaftor was generally well tolerated and had a safety profile consistent with that seen in TRAFFIC and TRANSPORT. In this 96-week safety extension study, all participants received one of two lumacaftor/ivacaftor combination regimens (400mg lumacaftor q12h in combination with 250mg ivacaftor q12h, or 600mg lumacaftor QD in combination with ivacaftor 250mg q12h). Mean lung function, a secondary endpoint of PROGRESS, was maintained above TRAFFIC/TRANSPORT baseline for up to 120 weeks. An analysis of the rate of lung function decline was also conducted at week 96 of PROGRESS to compare the results for people who received the approved commercial dose of lumacaftor (400mg q12h) in combination with ivacaftor (250mg q12h) (n=455) to a propensity score matched cohort (n=1,588) of patients from the US CFFPR.

The analysis showed that lumacaftor/ivacaftor reduced the estimated annual rate of lung function decline by approximately 42% compared with matched controls. The annual rate of lung function decline among those receiving lumacaftor/ivacaftor was -1.33% per year compared to the matched control group, which had a rate of decline of -2.29% per year (p < 0.001). The most common adverse events occurring in more than 20 percent of patients in either treatment group were pulmonary exacerbation, cough, sputum increased, haemoptysis, and dyspnoea. Mean blood pressure increased from 113.4/68.7 mmHg at baseline of TRAFFIC/TRANSPORT to 118.0/72.8 mmHg at week 96 of PROGRESS in patients continuing lumacaftor 400 mg q12h/ivacaftor and increased from 113.2/68.6 mmHg at baseline of TRAFFIC/TRANSPORT to 119.1/73.5 mmHg at week 96 of PROGRESS in patients who transitioned from placebo to lumacaftor 400 mg q12h/ivacaftor.