Date: 2015-10-14
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the 11th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS)
Company: Alnylam Therapeutics (USA - MA)
Product: ALN-TTRsc02
Action
mechanism: RNAi. ALN-TTRsc02 is a subcutaneous RNAi therapeutic targeting the transthyretin (TTR) gene. ALN-TTRsc02 utilizes Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc-siRNA conjugate delivery platform, which enables high potency and durability with a very wide therapeutic index.
Disease: transthyretin-mediated amyloidosis (ATTR)
Therapeutic area: Rare diseases - Genetic diseases
Country:
Trial details:
Latest
news: * On October 14, 2015, Alnylam Pharmaceuticals announced that it presented pre-clinical data and provided program guidance for ALN-TTRsc02, an investigational RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR amyloidosis). The new data were presented at the 11th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS), held October 11 - 14, 2015, in Leiden, Netherlands . In pre-clinical studies, including those in non-human primates (NHPs), ALN-TTRsc02 achieved potent and highly durable knockdown of serum TTR of up to 99% with multi-month durability achieved after just a single dose, supportive of a potentially once quarterly dose regimen. Based on these pre-clinical data, ALN-TTRsc02 is the most potent and durable investigational RNAi therapeutic discovered at Alnylam to date. The company is currently conducting Investigational New Drug (IND)-enabling studies and plans to file an IND or IND-equivalent in early 2016 with initial data in late 2016. Assuming positive clinical results, Alnylam expects to initiate a Phase 3 study for ALN-TTRsc02 in 2017.
In a presentation titled, "Enhanced Pharmacologic Activity and Durability Demonstrated with an ESC GalNAc-siRNA Targeting Transthyretin," Alnylam scientists presented data characterizing the development of ALN-TTRsc02. First, a series of ESC-GalNAc-siRNAs targeting TTR were screened for knockdown activity in transgenic mice and NHPs. These and other data led to selection of the Development Candidate (DC) for ALN-TTRsc02. In pharmacodynamic studies, ALN-TTRsc02 achieved potent and durable knockdown of serum TTR in transgenic mice and NHPs. In NHPs, a single subcutaneous dose at 1 mg/kg led to TTR knockdown of up to 99% with sustained knockdown of more than 50% for greater than 84 days. Monthly subcutaneous dosing at 1 mg/kg achieved sustained TTR knockdown of up to 99% with mean maximal effects greater than 95%. Data were also shown comparing TTR knockdown activity of ALN-TTRsc02 to that of revusiran, a late-stage, investigational RNAi therapeutic targeting TTR that utilizes Alnylam's first generation Standard Template Chemistry (STC)-GalNAc-siRNA conjugate technology. The results showed that ALN-TTRsc02 has a markedly superior TTR knockdown profile compared to revusiran. Finally, in initial rat toxicology studies, ALN-TTRsc02 was found to be generally well tolerated with no significant adverse events at doses as high as 100 mg/kg. Alnylam believes that these data, combined with the improved profile of ESC-GalNAc conjugates in humans compared to NHPs - as evidenced by clinical data from other Alnylam pipeline programs - may allow for a low dose, low volume, once quarterly subcutaneous dose regimen.
