Boston based Vertex Pharmaceuticals Incorporated Announced Phase 2 Results

Boston based Vertex Pharmaceuticals Incorporated announced Phase 2 proof-of-concept study, VX-864 achieved rapid, consistent and statistically significant increases in mean functional alpha-1 antitrypsin levels of 2.2 to 2.3 micromolar from baseline in people with alpha-1 antitrypsin deficiency with the PiZZ genotype, across three dose groups of VX-864 compared to placebo. Data provide evidence that an oral small molecule corrector constructed to promote the reasonable folding of the mutant Z-AAT protein can increase plasma levels of fAAT in patients with AATD.

Results provide proof-of-mechanism, the magnitude of treatment effect observed in this study is uncertain to translate into substantial clinical benefit. Vertex Pharmaceuticals Incorporated will not advance VX-864 into late-stage development and instead will advance additional novel small molecule correctors with the potential for increased clinical efficacy into the clinic.

The study met its primary endpoint, with all VX-864 dose groups demonstrating highly statistically increases in plasma fAAT levels from baseline compared to placebo at day 28 of treatment. Treatment with VX-864 resulted in a mean increase of 2.2 to 2.3 micromolar in fAAT levels across the three dose groups studied compared to placebo. All dose groups showed a rapid increase in fAAT by day 7 which was sustained over 28 days of treatment.

Similar statistical increases in antigenic AAT levels were observed compared to placebo, with a mean increase of 2.7 to 3.5 micromolar across the three dose groups studied. Plasma fAAT levels returned to baseline, in the 28-day safety follow-up period following VX-864 discontinuation, consistent with the half-life of native AAT protein and confirming the biological activity of VX-864. The primary outcome measures were the mean change from baseline in plasma fAAT levels at day 28 compared to placebo as well as safety and tolerability of VX-864.