Date: 2016-11-14
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the American Heart Association's Scientific Sessions 2016 in New Orleans
Company: Arrowhead Pharmaceuticals (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:
Therapeutic area: Cardiovascular diseases
Country:
Trial
details: * On November 14, 2016, Arrowhead Pharmaceuticals delivered oral presentations on ARC-LPA, its preclinical development program targeting lipoprotein (a), for the treatment of cardiovascular disease, at the American Heart Association's Scientific Sessions 2016 in New Orleans . The oral presentation titled, "Targeting apolipoprotein(a) with a novel RNAi delivery platform as a prophylactic treatment to reduce risk of cardiovascular events in individuals with elevated lipoprotein (a)", describes advancements in the preclinical development of ARC-LPA, which is part of a recently announced license and collaboration agreement with Amgen. Lp(a) levels in humans are genetically defined and higher levels correlate with increased risk of cardiovascular diseases, independent of cholesterol and LDL levels. Approximately 25% of the U.S. population has greater than 30 mg/dL of Lp(a) (normal levels: 0.1 - 25 mg/dL). It is predominantly expressed in the liver and circulates in blood.
Screening of LPA RNAi triggers in Lp(a) transgenic (Tg) mice identified several that induced substantial and sustained knockdown of serum Lp(a) levels
Structure activity relationship (SAR) studies assessing structure and chemical modifications identified triggers that achieved greater than 98% maximum knockdown after a single 3 mg/kg SQ dose in Tg mice
In NHPs, 85-90% reduction of serum Lp(a) levels was observed after three weekly 3 mg/kg SQ doses
In an atherosclerosis model, data suggest that RNAi triggers can be effectively delivered to a fatty liver using the DPCsqTM platform.
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