Date: 2016-05-06
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the Arteriosclerosis, Thrombosis and Vascular Biology | Peripheral Vascular Disease (ATVB|PVD) 2016 Scientific Sessions in Nashville
Company: Arrowhead Research Corporation (USA - CA)
Product: ARC-LPA
Action
mechanism: RNAi. ARC-LPA is a RNAi-based candidate designed to reduce production of apolipoprotein(a), a key component of lipoprotein(a), or Lp(a). Lp(a) levels in humans are genetically defined and higher levels correlate with increased risk of cardiovascular diseases, independent of cholesterol and LDL levels. ARC-LPA is Arrowhead's first drug candidate to use a subcutaneously administered delivery construct.
Disease: cardiovascular diseases
Therapeutic area: Cardiovascular diseases
Country:
Trial details:
Latest
news: * On May 6, 2016, Arrowhead Pharmaceuticals presented a poster on ARC-LPA, its preclinical development program targeting lipoprotein (a), or Lp(a), for the treatment of cardiovascular disease at the Arteriosclerosis, Thrombosis and Vascular Biology | Peripheral Vascular Disease (ATVB|PVD) 2016 Scientific Sessions in Nashville . ARC-LPA is the first RNAi therapeutic program to use Arrowhead's new delivery vehicles designed for subcutaneous (SQ) administration.
The poster titled, "Lipoprotein(a) targeting with RNAi delivery platforms in transgenic mice and cynomolgus monkeys" (presentation 428), describes data from in vitro screening of RNAi triggers and multiple in vivo models, including transiently transgenic mice, transgenic mice (Tg), and non-human primates (NHPs). Key findings from these studies include the following:
Screening of RNAi triggers in Tg mice identified those that exhibited substantial and sustained knockdown of serum apo(a) and Lp(a) levels
RNAi trigger sequences were active in both intravenous and SQ platforms.
Structure activity relationship (SAR) studies looking at chemical modifications to the RNAi trigger identified a lead that demonstrated greater than 98% maximum knockdown after a single 3 mg/kg SQ dose in transgenic mice.
Duration of effect gains were also made with greater than 85% knockdown still seen at 6 weeks post dose.
In NHPs, 85-90% reduction of serum Lp(a) levels was observed after three weekly 3 mg/kg SQ doses.
Duration of effect in NHPs was long, with Lp(a) levels still reduced by 75% 6 weeks after the final dose.
