Lung function was assessed by FEV1, which measures the amount of air a patient can forcibly exhale in one second. FEV1 is the measure of clinical benefit accepted by FDA and European regulators for the approval of new cystic fibrosis drugs.
Cystic fibrosis is a progressive disease that causes patients to typically lose about 1-2% of their lung function each year. Yet in Vertex's phase II study, the loss of lung function was accelerated in all patients in the first stage of the study.
From the start of the study through day 28, placebo patients lost almost 1% of their lung function but patients treated with high dose VX-809 alone lost almost 3% of their lung function in the same time period. In other words, VX-809-treated patients were faring worse than placebo.
In the second 28-day stage of the study, the lung function of placebo patients deteriorated by a further 2.5% but patients treated with Kalydeco added to high dose VX-809 rebounded dramatically with an improvement in lung function of 6.1%.Further evidence supporting the synergistic benefit of combining high dose VX-809 and Kalydeco was seen in the study's responder analysis. In the first 28 days of the study, 10% of cystic fibrosis patients treated with the high dose of VX-809 experienced an improvement in lung function of 5% or more. But when Kalydeco was added to VX-809 in the second 28 days of the study, the percentage of 5% or greater lung function improvers grew to 55%. Likewise, 5% of high dose VX-809 patients recorded a 10% improvement in lung function during the study's first stage, increasing to 25% when Kalydeco was added to VX-809 in the study's second stage. Vertex did not disclose responder analyses for patients treated with low- and mid-dose VX-809 plus Kalydeco. Wall Street expectations for the final results from the phase II study of VX-809 and Kalydeco appear to be largely met, based on a survey of institutional investors recently conducted by ISI Group bio-pharma analyst Mark Schoenebaum. The 119 investors surveyed, on average, expected to see a 6.7% improvement in placebo-adjusted lung function from the high dose VX-809 arm of the study. This is precisely what Vertex delivered.