PARSIPPANY, N.J.--(BUSINESS WIRE)--The Medicines Company (NASDAQ: MDCO) today announced positive topline results for the ORION-10 Phase 3 clinical study in patients with atherosclerotic cardiovascular disease (ASCVD), successfully completing the pivotal Phase 3 LDL-cholesterol (LDL-C) lowering clinical trials for inclisiran. ORION-10 met all primary and secondary endpoints, and inclisiran demonstrated efficacy, tolerability and safety that were at least as favorable as observed in ORION-11, with no treatment-related liver or renal laboratory abnormalities.
Detailed efficacy, tolerability and safety data from ORION-10 will be presented at the American Heart Association (AHA) Scientific Sessions in Philadelphia on Saturday, November 16, 11:06 am EST, during Late Breaking Science I: Outside the Box: New Approaches to CVD Risk Reduction. The company will also present data from the ORION-9 study in patients with Heterozygous Familial Hypercholesterolemia (HeFH) at the AHA congress on Monday, November 18, 9:24am EST, during Late Breaking Science VI: New Frontiers in Lipid Therapy.
“The results seen in ORION-10 again demonstrate inclisiran’s outstanding efficacy, tolerability and safety,” said Mark Timney, Chief Executive Officer of The Medicines Company. “This is further validation of the potential of this first and only investigational cholesterol-lowering therapy in the siRNA class to transform the treatment of cardiovascular disease for millions of people with ASCVD.”
The ORION program is studying the efficacy and safety of inclisiran in patients with ASCVD and FH, with ORION-9, ORION-10 and ORION-11 comprising the pivotal Phase 3 LDL-C lowering studies. The company announced topline results of ORION-9 in a separate news release today.
“The Medicines Company thanks the more than 3,600 patients and their dedicated clinical site teams who participated in the Phase 3 LDL-C lowering clinical program for inclisiran,” said Peter Wijngaard, Ph.D., Chief Development Officer of The Medicines Company. “Seeing such consistent results across the breadth of our clinical development program in patients treated with inclisiran for up to 3 years, including 18 months in pivotal Phase 3 studies, is truly impressive.
“We eagerly await the opportunity to present detailed study results during AHA and to also submit data for publication.”
Regulatory submissions for inclisiran are anticipated to occur in the U.S. in the fourth quarter of 2019 and in Europe in the first quarter of 2020. Patients who have completed their respective Phase 3 studies are now enrolling into ORION-8, an open-label, long-term extension study in which patients completing ORION-9, ORION-10 and ORION-11 will receive inclisiran for three years to generate longer-term efficacy, safety and tolerability data for inclisiran.
Background on Pivotal Phase 3 LDL-C Lowering Studies
ORION-9 is a pivotal Phase 3, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety and tolerability of inclisiran sodium 300 mg administered subcutaneously in 482 patients with clinical or genetic evidence of HeFH and elevated LDL-C, despite maximum tolerated dose of LDL-C-lowering therapies (e.g., a statin or ezetimibe). The primary endpoints are percentage change in LDL-C from baseline to day 510 (17 months) and time-adjusted percentage change in LDL-C from baseline between day 90 (three months) and up to day 540 (18 months). Key secondary endpoints include the mean absolute change at Day 510 (17 months), the average absolute reduction from Day 90 (three months) up to Day 540 (18 months), and changes in other lipids and lipoproteins. The international study was conducted at 54 sites in eight countries. Each study participant received inclisiran sodium 300 mg administered as a subcutaneous injection initially, again at three months and then every six months thereafter. The majority of study participants are taking inclisiran or placebo in addition to existing lipid-lowering therapy with a maximally tolerated statin (with or without ezetimibe).
ORION-10 is a pivotal Phase 3, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety and tolerability of inclisiran sodium 300 mg administered subcutaneously in 1,561 participants with ASCVD and elevated LDL-C, despite maximum tolerated dose of LDL-C-lowering therapies (e.g., a statin or ezetimibe). The primary endpoints are percentage change in LDL-C from baseline to day 510 (17 months) and time-adjusted percentage change in LDL-C from baseline after day 90 (three months) and up to day 540 (18 months). The majority of study participants are taking inclisiran or placebo in addition to existing lipid-lowering therapy with a maximally tolerated statin (with or without ezetimibe). Key secondary endpoints include the mean absolute change at Day 510 (17 months), the average absolute reduction from Day 90 (three months) up to Day 540 (18 months), and changes in other lipids and lipoproteins. The study was conducted at 145 sites in the United States. Each study participant received inclisiran sodium 300 mg administered as a subcutaneous injection initially, again at three months and then every six months thereafter. The majority of study participants are taking inclisiran or placebo in addition to existing lipid-lowering therapy with a maximally tolerated statin (with or without ezetimibe).
ORION-11 is a pivotal Phase 3, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety, and tolerability of inclisiran sodium 300 mg administered subcutaneously in 1,617 patients with ASCVD or ASCVD-risk equivalents and elevated LDL-C despite maximum tolerated dose of statin therapy (with or without ezetimibe). In ORION-11, twice-yearly dosing with inclisiran sodium 300 mg met all primary and secondary efficacy endpoints, was well-tolerated and demonstrated an excellent safety profile. Detailed study results were presented during a late-breaking science session at the European Society of Cardiology’s ESC Congress 2019 in Paris on September 2 [click here for news release].
About Inclisiran
Inclisiran, the first and only cholesterol-lowering therapy in the siRNA (small-interfering RNA or “sir-nah”) class, is The Medicines Company’s investigational twice-yearly therapy in Phase 3 clinical development to evaluate its ability to reduce low-density lipoprotein cholesterol (also known as LDL-C). As a siRNA, inclisiran harnesses the body’s natural process of RNA interference to specifically prevent production of the PCSK9 protein in the liver which enhances the liver’s ability to remove LDL-C from the bloodstream, thereby lowering LDL-C levels. Inclisiran is not yet approved for use by the FDA or any other regulatory authority. The Medicines Company obtained global rights to develop, manufacture and commercialize inclisiran under a license and collaboration agreement with Alnylam Pharmaceuticals.
Commercial Opportunity
Nearly 60 million people with ASCVD or FH across the U.S., the largest European countries, China and Japan are currently treated with lipid-lowering therapies to manage cardiovascular risk. More than 70 percent of these patients are not achieving LDL-C treatment goals with current therapies, and approximately two-thirds of patients do not adhere to available first-line cholesterol-lowering treatments after one year. This implies a population of more than 40 million people who could potentially benefit from the investigational candidate inclisiran in the aforementioned countries alone. Inclisiran is the first cholesterol-lowering siRNA with the potential to deliver potent and durable lowering of LDL-C levels via twice-yearly dosing that can help address two critical unmet needs – additional LDL-C lowering and poor adherence to therapy.
About The Medicines Company
The Medicines Company (NASDAQ: MDCO) is a biopharmaceutical company with a singular, relentless focus on addressing the greatest global healthcare challenge and burden today – cardiovascular disease. Our purpose is to halt the deadly progression of atherosclerosis and the cardiovascular risk created by high levels of LDL-C. The Company is headquartered in Parsippany, New Jersey. For more information, please visit www.themedicinescompany.com and follow us on Twitter @MDCONews and LinkedIn.
Forward-Looking Statements
Statements contained in this press release that are not purely historical, including, but not limited to, statements about the Company, the proposed offering described herein and the use of proceeds therefrom, are 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,” “should,” and “potential,” and similar expressions, are intended to identify forward-looking statements. These forward-looking statements involve known and unknown risks and uncertainties that may cause the Company’s actual results, levels of activity, performance or achievements to be materially different from those expressed or implied by these forward-looking statements. Important factors that may cause or contribute to such differences include the ability of the Company to effectively develop inclisiran; whether inclisiran will advance in the clinical trials process on a timely basis or at all, or succeed in achieving its specified endpoints; whether the Company will make regulatory submissions for inclisiran on a timely basis; whether its regulatory submissions will receive approvals from regulatory agencies on a timely basis or at all; the extent of the commercial success of inclisiran, if approved; the strength, durability and life of the Company’s patent protection for inclisiran and whether the Company will be successful in extending exclusivity; and such other factors as are set forth in the risk factors detailed from time to time in the Company’s periodic reports and registration statements filed with the SEC, including, without limitation, the risk factors detailed in the Company's Quarterly Report on Form 10-Q filed with the SEC on July 24, 2019. The Company specifically disclaims any obligation to update these forward-looking statements.
