Does Leqvio (Inclisiran) Affect Lp(a)? Clinical Evidence and Monitoring

What the Label Reports at Day 510

The efficacy table for Trial 1 (ORION-10) gives mean percentage change from baseline to day 510 for four lipid parameters: LDL-C, total cholesterol, non-HDL-C and apolipoprotein B [2]. On inclisiran, LDL-C fell 51% from baseline and ApoB fell 45%, against placebo-corrected differences of -52 and -43 percentage points [2].

The trial publications report LDL-C results in the same way. ORION-10 randomized 1,561 adults with atherosclerotic cardiovascular disease and ORION-11 randomized 1,617 adults with ASCVD or an ASCVD risk equivalent, all on maximally tolerated statin therapy, to inclisiran 284 mg or placebo on day 1, day 90 and every 6 months thereafter [1]. The placebo-corrected LDL-C change at day 510 was 52.3% in ORION-10 and 49.9% in ORION-11 [1]. In ORION-9, 482 adults with heterozygous familial hypercholesterolemia had LDL-C fall 39.7% on inclisiran and rise 8.2% on placebo at day 510, a between-group difference of -47.9 percentage points [3].

Lp(a) Is Not the Same Measurement as ApoB

Apolipoprotein B is one of the lipid parameters the Leqvio label reports. Lp(a) is a separate laboratory measurement, so a change in ApoB is not the same finding as a change in Lp(a), and the label's ApoB result cannot be read as an Lp(a) result [2].

How Inclisiran Lowers LDL-C

Inclisiran is a double-stranded small interfering RNA conjugated on the sense strand to triantennary N-acetylgalactosamine, which helps hepatocytes take it up. Inside the liver cell it directs catalytic breakdown of PCSK9 messenger RNA, which increases LDL receptor recycling and expression on the hepatocyte surface and lowers circulating LDL-C [2]. After doses on day 1 and day 90, mean serum PCSK9 fell about 75% at day 120 and 69% at day 180 [2].

Monitoring and Dosing on Leqvio

The label says to assess LDL-C when clinically indicated, and that the LDL-lowering effect may be measured as early as 30 days after the first dose and at any time after that, without regard to the timing of the dose [2]. The label gives the dosage as 284 mg as a single subcutaneous injection initially, again at 3 months, then every 6 months, administered by a healthcare professional into the abdomen, upper arm or thigh [2]. If a planned dose is missed by less than 3 months, the label says to give it and keep the original schedule; if missed by more than 3 months, it says to restart with the initial schedule [2].