Learning in liver
What hurdles companies must clear to crack liver-dominant AAT deficiency
Patients and caregivers at FDA's patient-focused drug development meeting on alpha-1 antitrypsin deficiency are desperate for treatments for liver-affected patients, whose only option is a transplant. With two RNAi programs now in the clinic and a possibility for expedited approval, a therapy could reach the market within five years -- but developers will first have to work with patients and regulators to develop trial designs for this poorly understood subset.
Alpha-1 antitrypsin (AAT; A1AT; SERPINA1) inhibits neutrophil elastase (ELANE; NE; HLE), which is secreted by neutrophils during inflammation to destroy bacteria. Alpha-1 antitrypsin deficiency (AATD) is caused by over 100 different mutations that result in misfolded or unfolded AAT, which is primarily synthesized in the liver. The disease affects about 150,000-200,000 patients in the U.S. and EU...