Inclisiran’s First Pivotal Trial Achieves Target Enrollment Ahead of Schedule
– ORION-11, a Phase III confirmatory clinical trial randomized more than 1,500 patients in 11 weeks –
FDA grants Orphan Drug Designation to inclisiran for the treatment of homozygous familial hypercholesterolemia (HoFH)
– Following encouraging Phase II data, a Phase III clinical trial of inclisiran in HoFH set to begin in 2018 –
PARSIPPANY, N.J. – January 25, 2018 – The Medicines Company (NASDAQ: MDCO) today announced that the target of 1,500 patients randomized in the ORION-11 trial has been exceeded in 11 weeks – considerably beating its goal of 28 weeks. ORION-11 is a double-blind, randomized Phase III trial designed to confirm the effectiveness and safety of inclisiran, an investigational agent which is potentially a first-in-class lipid-lowering drug, to reduce LDL-cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD) or cardiovascular risk-equivalents. In the trial, patients are randomized to inclisiran 300 mg or placebo given subcutaneously on days 1, 90, 270 and 450 – then followed to the end of the study at 540 days (18 months). ORION-11 is one of three similar trials designed to confirm inclisiran safety and effectiveness and potentially provide key data required for NDA and MAA submission in the United States and Europe. The other two trials (ORION-9 in heterozygous familial hypercholesterolemia and ORION-10 in ASCVD) are actively enrolling – also ahead of schedule – and are expected to complete enrollment during the first half of 2018. A fourth pivotal Phase III study in patients with HoFH is expected to enroll patients beginning later in 2018 and, following 6 months of treatment, to provide data for HoFH as part of a comprehensive LDL-C lowering program in a planned NDA and MAA submission.
The Company also affirmed its announcement, first made during its Investor Day on 23rd January, that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for inclisiran for the treatment of HoFH.
"Completion of enrollment in ORION-11 is a key milestone on our way to confirming the excellent safety and efficacy data for inclisiran," said David Kallend, MB BS, Chief Medical Officer of The Medicines Company. "We look forward to completing the follow-up of ORION-11 and the enrollment and follow-up of other pivotal trials, so that we can review the data in the second half of 2019 and potentially include the data in NDA and MAA submissions. We believe that the rapid pace of enrollment in ORION-11, as well as the quality of data emerging from this and other trials, reflect the design of the studies, the effective operational support of excellent clinical sites, and the apparent ease of use of the protocol and study medication."
Andrew Friedman, PharmD, Head of Regulatory Affairs at The Medicines Company added, "We are grateful for the FDA's review and grant of orphan drug designation for inclisiran. Based on the Phase II data, we believe inclisiran, an investigational new product, may have utility in patients with HoFH who carry a very high risk of ASCVD and mortality compared to most of the population. We will work with the FDA to complete the design and execution of a Phase III trial of inclisiran in HoFH patients and anticipate completion of the trial to include the results in an NDA planned for the end of 2019."
About ORION -11
ORION-11 is a Phase III, placebo-controlled, double-blind, randomized study of ~1,500 patients with ASCVD (coronary heart disease, cerebrovascular disease and peripheral arterial disease), or ASCVD-risk equivalents (e.g., type 2 diabetes, or 20% or greater risk of a cardiovascular event as assessed by Framingham risk score or equivalent), and elevated LDL-C levels above 70 mg/dL or 100 mg/dL respectively - despite maximum tolerated doses of LDL-C lowering therapies including statins. The primary endpoint of the study is LDL-C reduction from baseline to day 510. The trial also evaluates the safety and tolerability of inclisiran.
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 the terms of 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 FDA's Orphan Drug Designation program
The provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S. The Orphan Drug Act (ODA) provides for granting special status to a drug or biological product ("drug") to treat a rare disease or condition upon request of a sponsor. This status is referred to as orphan designation (or sometimes "orphan status"). For a drug to qualify for orphan designation both the drug and the disease or condition must meet certain criteria specified in the ODA and FDA's implementing regulations. Orphan designation qualifies the sponsor of the drug for various development incentives of the ODA, including tax credits for qualified clinical testing. A marketing application for a prescription drug product that has received orphan designation is not subject to a prescription drug user fee unless the application includes an indication for other than the rare disease or condition for which the drug was designated.
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 contained in this press 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" "expects" 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 whether clinical trials for inclisiran will advance on a timely basis, or at all, or succeed in achieving their specified endpoints; whether physicians will prescribe and patients will use inclisiran, if it becomes available; whether the Company will make additional regulatory submissions for inclisiran on a timely basis, or at all; whether the Company's regulatory submissions will receive approvals from regulatory agencies on a timely basis, or at all; and such other factors as are set forth in the risk factors detailed in the Company's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 9, 2017, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.