RARE Daily

Vertex Halts Development of Alpha-1 Antitrypsin Deficiency Therapy

October 15, 2020

Rare Daily Staff

Vertex Pharmaceuticals said it would stop dosing in a phase 2 trial and discontinue development of VX-814, its experimental therapy for alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disease that results in a lack of the protein AAT and can cause lung disease and liver disease as a result. VX-814 is an experimental small molecule drug that works to increase functional levels of alpha-1 antitrypsin.

The randomized, double-blind, placebo-controlled phase 2 study of approximately 50 patients was designed to evaluate the safety and pharmacokinetics of VX-814, and the ability of VX-814 to raise levels of alpha-1 antitrypsin over 28 days of dosing.

Elevated liver enzymes (AST/ALT) were observed in several patients. In four patients, across different doses studied, elevations greater than eight times the upper limit of normal were noted; the elevated liver enzymes have either resolved or are resolving.

Vertex stopped the study after it concluded that it would not be feasible to safely reach targeted exposure levels and achieve meaningful increases in AAT levels with VX-814.

“Based on the liver enzyme elevations observed, along with the determination that we would not be able to safely achieve targeted exposure levels with VX-814, we are discontinuing further development of this molecule,” said Carmen Bozic, executive vice president of global medicines development and medical affairs, and chief medical officer of Vertex.

The company is continuing to develop VX-864 and other molecules targeting the underlying cause of AATD.


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