Alnylam opens clinical trial application for ALN-TTRsc

Alnylam Pharmaceuticals has filed a Clinical Trial Application (CTA) with the UK Medicines and Healthcare products Regulatory Agency (MRHA) to start a clinical trial with ALN-TTRsc.

It is an RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR).

ALN-TTRsc is a subcutaneously administered therapeutic that includes a Sirna conjugated to a triantennary N-acetylgalactosamine (GalNAc) ligand.

GalNAc-siRNA conjugates are a proprietary Alnylam delivery platform and are engineered to accomplish targeted delivery of RNAi therapeutics to hepatocytes via uptake by the asialoglycoprotein receptor.

ALN-TTRsc is the first GalNAc-siRNA to enter clinical development stages, marking a significant milestone for Alnylam, which expects a phase 1 study of the solution to begin early this year, subject to approval of their CTA.

ATTR is an autosomal dominant inherited disease caused by mutations in the TTR gene, which is expressed mainly in the liver and leads to the accumulation of pathogenic deposits of mutant and wild-type TTR protein in a number of extra-hepatic tissues.

Pre-clinical studies have suggested that subcutaneous administration of ALN-TTRsc lead to a potent and sustained suppression of TTR.

The drug was taken in a loading dose regiment of once a day for five days, before a maintenance dose regimen of once a week for four weeks, culminating in an 80 per cent reduction of TTR at a dose as low as 2.5mg/kg.

Philip Hawkins, FMedSci., Professor of Medicine at University College London Medical School, said: "ATTR presents a tremendous unmet medical need and is an example of a disease caused by overproduction of a mutant protein. RNAi therapeutics represent a novel and compelling approach for the treatment of ATTR, as they have been shown to achieve robust knockdown of serum levels of both wild-type and mutant TTR."

Alnylam recently announced that it has presented new pre-clinical data from its RNAi therapeutic programme, which aims to boost treatments for haemophilia and other bleeding disorders.

It explained that new therapeutic options are required for patients with the disease. 

Posted by Ben Evans