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 86 th Annual European Atherosclerosis Society Congress
Analysis accepted for publication in Circulation, the Journal of the American Heart Association
Phase III trials of inclisiran progressing as planned with no material safety observations
The Medicines Company (NASDAQ:MDCO) today announced that the results of a pre-specified analysis of secondary endpoints from the ORION-1 Phase II study were presented at the 86 th European Atherosclerosis Society Congress (EAS 2018) and accepted for publication in Circulation, the journal of the American Heart Association.
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 Lisbon, Portugal, by the Principal Investigator for the ORION-1 and ORION-11 trials, Professor Kausik Ray, Professor of Public Health, Imperial College London, United Kingdom, and honorary consultant cardiologist, Imperial College NHS Trust. Professor Ray is the first author of the abstract accepted for publication in Circulation.
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, John J.P. Kastelein, M.D., Ph.D., Professor of Medicine and Chairman of the Department of Vascular Medicine at the Academic Medical Center of the University of Amsterdam, and Chairman of the ORION-1 and ORION-9, ORION-10 and ORION-11 Steering Committees, said, “Inclisiran had a powerful effect on these important secondary parameters of risk. Patient compliance is a huge issue in medicine, and there can be great variability in cholesterol levels when patients are required to take a treatment every day. However, inclisiran continues to work for months after each injection, with additional effects from follow-up doses. Some patients may get sufficient effects with a single dose, while those who need the most cholesterol reduction can be given two doses per year. Inclisiran could eventually become like a vaccine shot for people with high cholesterol.”
Dr. David Kallend, MBBS, Chief Medical Officer of The Medicines Company, said, “The data presented at EAS 2018 further confirm the robust and consistent efficacy of inclisiran’s dosing regimen on atherogenic lipoproteins across multiple patient populations and sub-groups, with no safety concerns observed in any patient population. We continue to be encouraged by the emerging safety information from our ongoing Phase III trials, which are generating five patient-years of inclisiran safety data each day.”
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.
The Medicines Company and Alnylam Pharmaceuticals, Inc. are collaborating in the advancement of inclisiran pursuant to their 2013 agreement. Under the terms of that agreement, Alnylam completed certain pre-clinical studies and the Phase I clinical study, with The Medicines Company leading and funding the development of inclisiran from Phase II forward, as well as potential commercialization.
About The Medicines Company
The Medicines Company is a biopharmaceutical company driven by an overriding purpose – to save lives, alleviate suffering and contribute to the economics of healthcare. The Company’s goal is to create transformational solutions to address the most pressing healthcare needs facing patients, physicians and providers in cardiovascular care. The Company is headquartered in Parsippany, New Jersey.
Statements in this presentation about The Medicines Company (the Company), the Company’s products and product candidates, the timing of clinical trial results, regulatory submissions, product or indication launches, the Company’s strategy, future financial results and operations, and future opportunities for the Company, that are not purely historical, and all other statements that are not purely historical, may be deemed to be forward-looking statements for purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words “believes," “anticipates," “plans,“ “expects," “intends," “estimates," “potential," “outlook,” “may,” “will,” “would,””could,” and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause actual results or events to differ materially from those indicated by such forward looking statements, including: whether the Company’s product candidate, inclisiran, will advance in the clinical trials process on a timely basis or at all; whether clinical trial results will warrant submission of applications for regulatory approval; whether the Company’s inclisiran will receive approvals from regulatory agencies; the extent of the commercial success of inclisiran, if approved; and such other factors as are set forth in the risk factors detailed from time to time in the Company’s periodic reports filed with the Securities and Exchange Commission (SEC) including, without limitation, the risk factors detailed in the Company’s Annual Report on Form 10-K filed with the SEC on March 1, 2018, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements whether as a result of new information, future events or otherwise.
The Medicines Company
Krishna Gorti, M.D., 973-290-6122
Vice President, Investor Relations