This rapid fire session highlighted six important emerging and experimental therapies that are expected to someday soon change the management of lipid disorders and prevention of cardiovascular disease.
Session: Non-LDL-C Targets: Triglycerides, Remnant Lipoproteins, and Other – Lp(a)
Presenter: Børge G. Nordestgaard, MD, DMSc
- New and ongoing trials are investigating triglyceride-lowering therapy to reduce residual major atherosclerotic cardiovascular event risk after statin treatment.
Session: Newly Approved Treatment with Bempedoic Acid for LDL Cholesterol Lowering
Presenter: Anne Carol Goldberg, MD
- Bempedoic acid is a once daily, first-in-class, small molecule that lowers LDL-C, with reduction hitting around 15 to 25%.
- This may be a new tool among lipid lowering medications, as it inhibits ATP citrate lyase, a step in the cholesterol synthesis pathway.
- Well tolerated in clinical trials, Bempedoic is a pro-drug that’s converted to active form in the liver.
- Safety and efficacy for cardiovascular risk reduction will be tested in the cardiovascular outcomes trial.
Session: Experimental Lipid Lowering with Evinacumab
Presenter: Zahid Ahmad, MD
- The FDA designated Evinacumab breakthrough status.
- In 142 individuals who were healthy or with mild hypertriglyceridemia, Evinacumab reduced triglycerides by 70 to 80%
- Ongoing phase II and phase III trials are investigating long-term safely and efficacy in severe hypertriglyceridemia.
Session: Experimental Treatment with Inclisiran
Presenter: Karol Watson, MD, PhD
- Inclisiran is a long-acting, small interfering RNA that inhibits the synthesis of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9).
- Inclisiran lowers LDL cholesterol impressively and durably.
- One subcutaneous administration of inclisiran at a 300 mg dose led to a reduction in LDL-C by more than 50% and four inclisiran injections over 18 months led to sustained LDL-C lowering.
- Inclisiran was safe and well tolerated with an adverse event profile similar to a placebo.
Session: Experimental Therapy for Apolipoprotein CIII Lowering: ASO and siRNA
Presenter: Rosanne Crooke, PhD
- RNA-targeted drugs (TRDs) provide a direct route from genomic information to patient, with ideal modalities to selectively inhibit genetically validated targets, like apoC-III.
- Three RTDs are currently advancing in the clinic:
- Two antisense drugs, Volanesorsen and AKCEA-APOCIII
- One siRNA drug, ARO-APOC3
Session: Experimental Therapy for LP(a) Lowering
Presenter: Sam Tsimikas, MD, FAHA
- RNA therapeutics are idealy suited to reduce production of apo(a) in hepatocytes and to prevent assembly of Lp(a).
- Antisense oligonucleotides to apo(a) are highly effective in reducing Lp(a) to non-atherogenic level, with no safety signals in a phase II trial of treatment duration of up to 1 year.
- The phase III HORIZONS trial is set to test the hypothesis that lowering Lp(a) will lead to clinical benefit.