Interim results from ongoing ORION-3 study demonstrated sustained lowering of LDL-C by more than 50 percent, with time-averaged absolute reductions of 59.4 mg/dL
No material safety issues observed in the study
Pivotal Phase 3 readouts for inclisiran expected in 3Q-2019 followed by regulatory filings expected in the U.S. in 4Q-2019 and Europe in 1Q-2020
New Long-Term Data Show that Twice-a-Year Dosing with Inclisiran Results in Persistent Lowering of LDL Cholesterol with No Material Safety Observations Out to Three Years
The Medicines Company (NASDAQ: MDCO) today announced interim results from the ongoing ORION-3 open-label extension study (Group 1, n=290) which showed that twice-a-year dosing with inclisiran sodium 300 mg resulted in consistent lowering of low density lipoprotein cholesterol (LDL-C) by more than 50 percent with overall follow-up of up to three years. Inclisiran was well tolerated, and no material safety issues were observed in the study. These results were presented today during a late-breaking clinical trial session at the National Lipid Association (NLA) Scientific Sessions in Miami.
Inclisiran, the first cholesterol-lowering therapy in the siRNA class, is in Phase 3 clinical development to evaluate its ability to lower LDL-C through twice-a-year dosing. Pivotal Phase 3 readouts for inclisiran are expected in the third quarter. ORION-3 (n=382) is an open-label extension study of the Phase 2 ORION-1 trial to assess the efficacy, safety and tolerability of long-term dosing of inclisiran.
“The cumulative effects of elevated LDL-C over time continue to place millions of people with atherosclerosis at increased cardiovascular risk, despite the widespread use of LDL cholesterol-lowering treatments,” said John J.P. Kastelein, M.D., Ph.D., ORION-3 study chair and Professor of Medicine at the Department of Vascular Medicine at the Academic Medical Center of the University of Amsterdam, The Netherlands. “These new data from ORION-3 provide further evidence of inclisiran’s unprecedented ability to deliver persistent LDL-C reductions over a prolonged period, which can help more patients reliably achieve LDL-C goals. Inclisiran also demonstrated a favorable safety profile, an important consideration given the long duration of LDL-C treatment.”
In this interim analysis of ORION-3, inclisiran demonstrated a 51 percent (64.0 mg/dL, p<0.001) reduction in LDL-C levels through day 210, which was the study’s primary endpoint. The time-averaged absolute LDL-C reduction with inclisiran was 59.4 mg/dL (p<0.001). These effects were independent of dose level and number of doses of inclisiran previously given in the ORION-1 study.
With overall follow-up of approximately three years from the first dose in ORION-1, no change in the overall safety profile was observed in this interim analysis of ORION-3 compared to the one-year follow-up in ORION-1. Inclisiran was well tolerated and no material safety issues were observed, including no elevations of liver enzymes or changes in renal function considered related to study medication. Clinically relevant injection site reactions were infrequent, mild or moderate, and transient, in line with observations in ORION-1.
“The strong data from ORION-3 bolster our confidence in inclisiran’s robust therapeutic profile which offers a vastly different value proposition compared to any other LDL-C lowering option,” said Mark Timney, Chief Executive Officer of The Medicines Company. “We truly believe that inclisiran could be a game-changer in cardiovascular care, providing simplicity and confidence to the treating physician and the treated patient that LDL cholesterol is lowered.”
“These new results reinforce that the potent, durable and consistent LDL-lowering effects of inclisiran continue over the long term with twice-a-year dosing that we believe can address the challenges of treatment adherence through improved therapeutic coverage and persistence,” said Peter Wijngaard, Ph.D., Chief Development Officer of The Medicines Company. “We also remain encouraged by inclisiran’s safety profile.”
More than 3,000 patient-years of inclisiran safety data have been accumulated to date in the ORION program. The data from ORION-3, as well as ongoing review of blinded data to date from the Phase 3 trials, show no material safety issues; data are at least as favorable as those generated and published from the ORION-1 Phase 2 trial.
Background on ORION-1 and ORION-3
ORION-1 is a Phase 2, placebo-controlled, double-blind, randomized trial to evaluate the efficacy, safety, and tolerability of inclisiran in participants with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents and elevated LDL-C despite maximum tolerated dose of LDL-C lowering therapies.
Subjects who completed ORION-1 and met all inclusion and exclusion criteria enrolled into ORION-3 in two groups. In Group 1, subjects (n=290) previously treated with any inclisiran dose in ORION-1 received twice-a-year injections of inclisiran sodium 300 mg. The ORION-3 primary endpoint was mean percent change in LDL-C from the ORION-1 baseline value, measured at day 210 in Group 1. The interim analysis of ORION-3 presented on May 18, 2019, reported safety and efficacy of inclisiran for Group 1 only (NLA Scientific Sessions, “Long-term twice-a-year dosing of inclisiran, a novel siRNA therapy, results in persistent LDL-C lowering in Phase II extension study (ORION-3),” speaker: John J. P. Kastelein, M.D., Ph.D.).
In Group 2, subjects (n=92) previously treated with placebo in ORION-1 received one year of treatment with evolocumab (140 mg injections every two weeks) followed by three years of treatment with inclisiran sodium 300 mg given on day 360 and 450 and every six months thereafter. For Group 2, safety and efficacy of switching from evolocumab to inclisiran will be assessed in an exploratory manner. Follow up for Group 2 is ongoing, and completion is projected to occur in 2022 followed by anticipated presentation of data in a scientific forum.
Investor Conference Call and Webcast Information
The Company will host a conference call and webcast today at 5:30 p.m., U.S. Eastern Standard Time. During the call, the Company’s management and clinical trial investigators will discuss interim results from the ongoing ORION-3 study. The dial-in information to access the call is as follows immediately below. A live audio webcast of the conference call may be accessed in the “Investors & Media” section of The Medicines Company website.
U.S./Canada: (877) 407-0312
International: (201) 389-0899
Conference ID: 13690839
A taped replay of the conference call will be available for approximately one week. The replay may be accessed as follows immediately below. An archived webcast will be available after the call concludes.
U.S./Canada: (877) 660-6853
International: (201) 612-7415
Conference ID: 13690839
Inclisiran, the first cholesterol-lowering therapy in the siRNA class, is The Medicines Company’s investigational therapy in Phase 3 clinical development to evaluate its ability to lower low-density lipoprotein cholesterol (also known as LDL-C or bad cholesterol) through twice-a-year dosing. As a siRNA, inclisiran directly targets messenger RNA and harnesses one of the body’s powerful natural mechanisms, RNA interference, to prevent production of the PCSK9 protein at its source in the liver and facilitate removal of LDL-C from the bloodstream. In Phase 2 studies, inclisiran provided clinically significant LDL-C reductions greater than 50 percent in addition to the effects of statins and/or ezetimibe, and LDL-C reductions were sustained throughout the six-month dosing interval. 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.
In the U.S. alone, approximately 15.1 million people are currently treated with lipid-lowering therapies to manage cardiovascular risk, but only one out of five (or 2.4 million) is successfully reaching LDL-C targets with current therapies. This implies a population of at least 12.7 million Americans who could potentially benefit from the investigational candidate inclisiran, the first cholesterol-lowering siRNA with the potential to deliver potent, durable and consistent lowering of LDL-C levels via twice-a-year dosing.
Statements contained in this news release about The Medicines 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,” “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 Securities and Exchange Commission (SEC), including, without limitation, the risk factors detailed in the Company's Quarterly Report on Form 10-Q filed with the SEC on April 26, 2019, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.
Today $MDCO announced positive interim results from the ongoing ORION-3 study in patients with high #cardiovascular risk and elevated LDL-C. #cholesterol