18 April 2019 - - US-based Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) has received clearance from the US Food and Drug Administration to proceed with an adaptive Phase 2/3 trial with the potential to serve as a pivotal registrational study of ARO-AAT, the company's second generation subcutaneously administered RNA interference therapeutic being developed as a treatment for a rare genetic liver disease associated with alpha-1 antitrypsin deficiency, the company said.

Arrowhead intends to initiate the adaptive design, Phase 2/3 study of ARO-AAT in patients with AATD associated liver disease at various sites in the US in 2Q19, followed by various international sites in Europe, pending regulatory submission and review.

The proposed primary objectives are to evaluate safety and pharmacodynamic dose response, and to evaluate efficacy, defined as an improvement in a histologic grading scale of AATD associated liver disease, and no worsening of liver fibrosis based on Ishak score on end of study biopsy. The company plans to provide additional study details following its initiation.

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them.

Using a portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes.

RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead's RNAi-based therapeutics leverage this natural pathway of gene silencing.