PARIS--(BUSINESS WIRE)--The Medicines Company (NASDAQ: MDCO) today announced the presentation of results from ORION-11, its first pivotal Phase 3 clinical study of inclisiran, an investigational twice-yearly therapy to reduce low-density lipoprotein cholesterol (LDL-C) and the first and only cholesterol-lowering therapy in the siRNA (small-interfering RNA or “sir-nah”) class. 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. Full study results were presented today during a late-breaking science session at the European Society of Cardiology’s ESC Congress 2019 in Paris.
“The cumulative effects of long-term uncontrolled LDL-C continue to place millions of people at increased cardiovascular risk,” said Kausik Ray, M.D., principal investigator of ORION-11, professor of public health and Consultant Cardiologist at Imperial College London. “The results of the ORION-11 trial support the unprecedented potential of inclisiran to deliver assurance to clinicians and patients that LDL-C can be lowered in a sustained fashion over the long-term with an infrequent dosing regimen and an excellent safety profile. This is a groundbreaking new approach for preventing atherosclerotic cardiovascular disease with exciting implications at a population health level.”
For the primary endpoints of ORION-11, inclisiran delivered placebo-adjusted LDL-C reductions of 54% (p<0.0001) at day 510 and demonstrated time-averaged placebo-adjusted LDL-C reductions of 50% (p<0.0001) from days 90 through 540.
The overall adverse event profiles of the placebo- and inclisiran-treated groups in ORION-11 were similar. A similar proportion of patients in the placebo- and inclisiran treated groups experienced at least one serious treatment emergent adverse event (22.5% vs. 22.3%). The incidence of deaths (1.9% vs. 1.7%) and malignancies (2.5% vs 2.0%) was similar between the placebo and inclisiran groups, respectively. A difference between placebo and inclisiran was observed in the incidence of fatal and non-fatal myocardial infarctions (2.7% vs. 1.2%) and fatal and non-fatal strokes (1.0% vs. 0.2%).
Clinically relevant elevations in liver function tests (ALT 0.5% vs. 0.5%, AST 0.5% vs. 0.2%) and serum creatinine increases (1.4% vs. 0.6%) were similar between the placebo and inclisiran groups, respectively. The incidence of clinically relevant injection site reactions between the placebo and inclisiran groups was infrequent (0.5% vs. 4.7%), with events predominantly mild and transient.
“The exceptional data from ORION-11 show that inclisiran delivers durable and potent LDL-C reductions through twice-yearly dosing that we believe can address adherence challenges in a way that no other currently used LDL-C lowering medicine can,” said Mark Timney, Chief Executive Officer of The Medicines Company. “We are excited at the prospect of bringing forward a remarkable, transformative advance in the treatment of cardiovascular disease.”
ORION-11 data will be submitted to a peer-reviewed medical journal. The sequential release of topline Phase 3 data readouts for the ORION-9 and ORION-10 studies is expected to continue later in the third quarter in advance of anticipated regulatory submissions 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 where patients completing ORION-9, ORION-10 and ORION-11 will receive inclisiran for three years to evaluate the efficacy, safety and tolerability of long-term dosing of inclisiran.
ORION-11 Study Design
The efficacy and safety of inclisiran in patients with atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia is being studied in the ORION clinical trial program.
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). The international study was conducted at 70 sites in seven countries (ex-US).
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 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). 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 population enrolled in ORION-11 was representative of a high-risk cohort of ASCVD and risk-equivalent patients, with a balanced randomization between placebo and inclisiran. Mean age was 65, and 87% of patients had diagnosed ASCVD, with remainder (13%) diagnosed with ASCVD risk equivalents. Average baseline LDL-C at study day 1 was 106 mg/dL across the study population. Nearly all patients (96%) were taking underlying statins, with the majority on high-intensity statins (90%).
ORION-11 Investor Conference Call and Webcast Information
The Medicines Company will host a conference call and webcast on Monday, September 2, 2019 at 8:00 a.m., Eastern Daylight Time (2:00 p.m., Central European Time). During the call, the Company’s management and ORION-11 principle investigator Prof. Kausik Ray will discuss results of the ORION-11 study. The dial-in information to access the call is as follows:
U.S./Canada: |
(877) 407-0312 |
International: |
(201) 389-0899 |
Conference ID: |
13692300 |
A taped replay of the conference call will be available after the call concludes, and may be accessed by telephone as follows:
U.S./Canada: |
(877) 660-6853 |
International: |
(201) 612-7415 |
Conference ID: |
13692300 |
A live audio webcast of the conference call may be accessed in the “Investors” section of The Medicines Company website. An archived webcast will be available after the call concludes.
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 familial hypercholesterolemia 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,” “would,” 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.
