ODYSSEY OUTCOMES trial

• Compared with placebo in patients with recent acute coronary syndrome (ACS), alirocumab 75 or 150 mg subcutaneous Q2W targeting LDL-C levels 25-50 mg/dL and allowing levels as low as 15 mg/dL:

o   Reduced major adverse cardiovascular events (MACE), myocardial infarction (MI) and ischemic stroke

o   Was associated with a lower rate of all-cause death

o   Was safe and well-tolerated over the duration of the trial.

• Lipoprotein(a) [Lp(a)] reduction in persons with CVD:

o   APO(a)-LRx reduced Lp(a) levels in a dose-dependent manner in patients who had elevated Lp(a) levels and established CVD.

o   There were no significant differences between any APO(a)-LRx dose and placebo with respect to platelet counts, liver and renal measures, or influenzalike symptoms.

o   The most common adverse events were injection-site reactions.

Single ascending dose study of small interfering RNA (siRNA) targeting Lp(a) production in individuals with elevated plasma Lp(a) levels:

• Subcutaneous injection of an siRNA (SLN360) targeting mRNA for the LPA gene lowered Lp(a) up to 98%.
• >70% and >80% reductions in Lp(a) persisted for 150 days after the 300 mg and 600 mg doses.
• The highest doses reduced LDL-C and apoB by 20% to 30%.
• There were no major safety issues, although low-grade, transient, dose-dependent injection site reactions occurred. These findings support the further development of this therapy.

PCSK9 inhibitor therapy with inclisiran

• Inhibition of PCSK9 inhibitor with inclisiran is a very promising and potentially the simplest and most effective approach to further reducing LDL-C, the cause of atherosclerosis.

o   LDL-C variability within individuals is practically eliminated.

o   Injection burden reduced substantially.

o   Sustained effect between infrequent injections

o   Opportunity to improve patient adherence.

• Phase II and the ongoing Phase III studies have robust long-term efficacy with no safety issues.