Alnylam Pharmaceuticals has started the Phase I / II clinical trial with ALN-AAT, a subcutaneously administered investigational RNAi therapeutic targeting alpha-1 antitrypsin (AAT) to treat AAT deficiency-associated liver disease (alpha-1 liver disease).

ALN-AAT is a subcutaneously administered investigational RNAi, which uses the firm’s ESC-GalNAc-siRNA conjugate delivery technology.

Initially, the study will be carried out in normal healthy volunteers and then in patients with alpha-1 liver disease. The trial is being conducted based on pre-clinical data presented during Digestive Disease Week (DDW).

Alnylam Pharmaceuticals R&D executive president and chief medical officer Dr Akshay Vaishnaw said: "We believe ALN-AAT has the potential to be a transformative therapy for patients with alpha-1 liver disease, an increasingly recognised clinical manifestation of alpha-1 antitrypsin deficiency where liver transplantation is the only available treatment option."

"We believe ALN-AAT has the potential to be a transformative therapy for patients with alpha-1 liver disease."

The trial is a randomised, single-blind and placebo-controlled study that is being carried out in three parts, including Part A, B and C.

Parts A and B are single-dose and multi-dose and dose-escalation studies that will enrol up to a total of 48 healthy adult volunteers.

Part C will be a multi-dose study that will enrol up to a total of 24 adults with alpha-1 liver disease and mild-to-moderate liver fibrosis.

According to the firm, the primary objective of the study is to assess safety and tolerability of single and multiple subcutaneous doses of ALN-AAT and secondary objectives comprise evaluation of pharmacokinetics and clinical activity for ALN-AAT as measured by knockdown of serum AAT.

In January 2014, Alnylam partnered with Sanofi firm Genzyme to enhance the development and commercialisation of RNAi therapeutics worldwide.