The Medicines Company Announces Inclisiran Data Showing Significant Reductions in Potentially Harmful Subtypes of Bad Cholesterol (Atherogenic Lipoproteins) Linked to Heart Attack and Stroke
Inclisiran reduced key atherogenic lipoproteins – found in the blood of individuals at high risk of heart attacks – back to normal in 68% to 90% of patient studied
Inclisiran drove sustained lowering of key atherogenic lipoproteins – non-HDL-C, ApoB, VLDL-C and Lp(a)
Pre-specified analysis of ORION-1 Phase II study featured in
late-breaking session at 86th Annual
Analysis accepted for publication in Circulation, the
Phase III trials of inclisiran progressing as planned with no material safety observations
Investigators examined inclisiran’s effects beyond LDL-C and showed that it also reduces atherogenic lipoproteins in a profound and sustained manner. Atherogenic lipoproteins – non-HDL-C, ApoB, VLDL-C and Lp(a) – have each been associated with an increased risk of heart attacks and strokes, particularly in high-risk patients. The reductions, which were generally dose-dependent, were achieved most clearly with a 300 mg dose of inclisiran given on Day-1 and Day-90, and were sustained to the pre-specified time of assessment (180 days) and beyond (at least 210 days). This is the same starting dose of inclisiran being utilized in the Phase III trials (the Phase III dose of inclisiran is 300 mg given on Day-1 and Day-90 and then every six months thereafter). The Phase III trials, which are assessing a range of markers of disease risk, including LDL-C as the primary endpoint and other atherogenic proteins as secondary endpoints, are expected to report results in the second half of 2019.
The new findings were presented in a late-breaking session at EAS 2018,
being held in
Commenting on the findings, Professor Ray said, “This completes the picture of inclisiran’s effects on bad cholesterol – so called atherogenic lipoproteins. The data are quite similar to those for monoclonal antibodies directed against PCSK9. We know that elevated LDL cholesterol carries an increased risk for patients, but it does not account for all 'bad cholesterol'. While we encourage patients to make lifestyle changes, such as exercising regularly and eating a healthy diet, if we are looking solely at LDL cholesterol, we may be underestimating risk. In ORION-1, we found that inclisiran was able to reduce non-HDL cholesterol and other atherogenic lipoproteins, such as Apolipoprotein B, in a significant and sustained way.”
In the presentation, Professor Ray reported that the selected starting dose for inclisiran in the Phase III trials achieved guideline-recommended goals for ApoB and non-HDL-C for high- and very high-risk patients in 68% to 90% of patients, compared to 25 to 49% of patients given placebo (all p-values <0.0001 - see table) This effect was highly consistent across patients and stable and sustained for up to 210 days after initial treatment.
Two inclisiran starting doses
Percent of patients achieving goal at Day-180
|Parameter||Goal||Placebo||Inclisiran 300 mg|
|All comparisons to placebo p-value <0.0001|
Commenting on the data,
ORION-1 was a placebo-controlled, double-blind, randomized Phase II trial of single or multiple subcutaneous injections of inclisiran in a total of 501 patients with atherosclerotic cardiovascular disease (ASCVD), or ASCVD-risk equivalents (e.g., diabetes and familial hypercholesterolemia), and elevated LDL-C despite maximum tolerated doses of LDL-C lowering therapies. The trial compared the effect of different doses of inclisiran and evaluated the potential for an infrequent dosing regimen. The primary endpoint of the trial was the percentage change in LDL-C from baseline at Day-180.
Inclisiran is an investigational GalNAc-conjugated RNA interference therapeutic, which inhibits the synthesis of PCSK9 protein in liver cells, thereby reducing liver cell LDL-receptor turnover, and lowering plasma LDL-C.
Statements in this presentation about The
The Medicines Company
Krishna Gorti, M.D., 973-290-6122
Vice President, Investor Relations