Vertex Pharmaceuticals of Cambridge, Mass., has released a correction to the previously reported responder analysis, as well as additional data from, its recent interim analysis of an ongoing phase II combination study of VX-809 and Kalydeco (ivacaftor) that showed significant improvements in lung function (forced expiratory volume in one second, FEV1) among adults with cystic fibrosis who have two copies of the most common mutation in the cystic fibrosis transmembrane conductance regulator gene, F508del.
On May 7, 2012, the company announced that approximately 46% (17/37) of patients with two copies of the F508del mutation experienced an improvement in lung function (FEV1) of five percentage points or more and approximately 30% (11/37) experienced an improvement of 10 percentage points or more from baseline to Day 56 when treated with the combination of VX-809 and Kalydeco. These results were relative improvements, not absolute improvements as originally reported.
The actual absolute improvements in lung function for these patients are: approximately 35% (13/37) experienced an absolute improvement of five percentage points or more and approximately 19% (7/37) experienced an absolute improvement of 10 percentage points or more from baseline to Day 56. As previously announced, none of the patients treated with placebo (0/11) achieved a five percentage-point or more mean absolute improvement in lung function from baseline to Day 56.
With Vertex’s announcement of incorrect data, its stocks, which had risen 86% since the initial release of data on May 7, fell by nearly 15% to $55.20.
However, the corrected data still demonstrates a statistically significant improvement in lung function (absolute change in percent predicted FEV1). A mean absolute improvement in lung function of 8.5 percentage points was observed among those who were treated with VX-809 and Kalydeco compared to placebo (p=0.002). In addition, the within-group mean absolute improvement from baseline to Day 56 was 4.0 percentage points (p=0.002) for patients treated with the combination. From baseline to Day 56, those treated with placebo experienced a mean absolute decrease in lung function of 4.6 percentage points (p=0.04).
These data are from a planned interim analysis that was conducted after approximately half of the patients completed 56 days of treatment. Evaluation of patients with one copy (heterozygous, n=21) of the F508del mutation is ongoing. All patients have now completed dosing. Analyses are ongoing and complete data, including statistical analyses for all patient groups, will be available mid-year. Vertex plans to start a pivotal study of VX-809 and Kalydeco in people with two copies of the F508del mutation, pending final study results and discussions with regulatory agencies.