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.
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.