Vertex Pharmaceuticals shares plummeted as the Boston-based company stopped the VX-814 Phase 2 trial. This randomized, double-blind, placebo-controlled study including approximately 50 patients was designed to investigate the safety and pharmacokinetic (PH) profile of VX-814 and its ability to boost functional levels of alpha-1 antitrypsin over 28 days of dosing. Elevated liver enzymes (AST/ALT) were observed in several patients. In fact, in four patients across different doses studied, elevations greater than 8 times the upper limit of normal were observed. Based on this and other findings, Vertex concluded that it was not feasible to safely research the targeted exposure levels, and thus meaningful increases in AAT, and hence VX814 was halted.
The Phase 2 trial (NCT04167345) was designed to treat a rare liver and lung disease known as alpha-1 antitrypsin deficiency, or AATD. However, the prospect of liver toxicity was too high.
Alpha-1 Antitrypsin Deficiency
Alpha-1 antitrypsin deficiency (AAT deficiency) is an inherited condition that raises your risk for lung and liver disease. Alpha-1 antitrypsin (AAT) is a protein that protects the lungs—the liver makes it. If the AAT proteins aren’t the right shape, they get stuck in the liver cells and can’t reach the lungs.
For more on this study, follow the link to the company’s press release.