The Medicines Company Completes Patient Enrollment for ORION-1 Study of PCSK9si
The Medicines Company (NASDAQ:MDCO) has announced the completion of patient enrollment in the ORION-1 study of PCSK9si, its investigational first-in-class RNA interference (RNAi) proprotein convertase subtilisin/kexin type 9 synthesis inhibitor (PCSK9si).
The study – which started enrolling in January 2016 – met its target of enrolling 480 patients with high cardiovascular risk and elevated LDL-C ahead of schedule. Follow-up of these patients will track the effects of different dosages of PCSK9si on LDL-C. A previous study showed that a single dose of PCSK9si lowered LDL-C significantly for six months - supporting the potential for subcutaneous dosing as infrequently as twice a year. Experts believe that such a dosing schedule could significantly improve patient adherence to treatment. Patient adherence to current treatments for elevated levels of bad cholesterol is recognized as a major problem in cardiovascular health management.
Interim three-month and six-month effectiveness and safety data from patients in ORION-1 are expected to be available, analyzed and presented by the end of 2016.
“We and our partners at Alnylam are pleased to have completed enrollment of ORION-1. We believe that PCSK9si has significant potential given its highly competitive profile as compared with anti-PCSK9 monoclonal antibodies (MAbs), a recently approved class of LDL-C lowering drugs. Indeed, in our view, the potential for management of hypercholesterolemia with two injections per year could be a transformative option for patients, physicians, and payers in the treatment of atherosclerotic cardiovascular disease (ASCVD),” said David Kallend, MBBS, Vice President and Global Medical Director, The Medicines Company. “Assuming positive data from ORION-1, we are on track to initiate Phase 3 registration studies in early 2017. In addition, we plan on conducting studies directly comparing PCSK9si with anti-PCSK9 MAbs as well as studies in homozygous familial hypercholesterolemia starting this year, to confirm the important features and potential benefits of this first-in-class investigational PCSK9 synthesis inhibitor.”
ORION-1 is a placebo-controlled, double-blind, randomized Phase II trial of single or multiple subcutaneous injections of PCSK9si 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 study compares the effect of different doses of PCSK9si and evaluates the potential for a quarterly or bi-annual dosing regimen. The primary endpoint of the study is the percentage change in LDL-C from baseline at Day 180.
An interim evaluation with Day 90 follow-up for all subjects will be conducted with the intention of presenting these data at a major cardiology conference in Q4 of this year. The company expects to complete Day 180 follow-up in all patients for the primary endpoint evaluation in early December.
PCSK9si (also known as ALN-PCSsc) is an investigational GalNAc-conjugated RNAi therapeutic targeting PCSK9 – a genetically validated protein regulator of LDL receptor metabolism – being developed for the treatment of hypercholesterolemia. In contrast to anti-PCSK9 monoclonal antibodies (MAbs) that bind to PCSK9 in blood, PCSK9si is a first-in-class investigational medicine that acts by turning off PCSK9 synthesis in the liver.
In a previous single ascending dose study, PCSK9si was associated with maximal PCSK9 knockdown of 88.7 percent with mean maximum knockdown of up to 82.3 ± 2.0 percent and maximal LDL-C reduction of 78.1 percent with mean maximum lowering of up to 59.3 ± 5.0 percent. At Day 180, a single dose of PCSK9si was associated with an up to 53 percent reduction in LDL-C, with a least squares mean percent lowering of 47.0 percent in the 300 mg dose cohort.
In a previous multiple ascending dose study, PCSK9si was associated with maximal PCSK9 knockdown of 94.4 percent with mean maximum knockdown of up to 88.5 ± 1.6 percent and maximal LDL-C reduction of 83.0 percent with mean maximum lowering of up to 64.4 ± 5.4 percent.
PCSK9si was generally well tolerated following single and multiple subcutaneous dose administration, with no serious adverse events (SAEs) or discontinuations due to AEs.
The Medicines Company and Alnylam Pharmaceuticals are collaborating in the advancement of PCSK9si per the companies’ agreement formed in early 2013. Under the terms of the agreement, Alnylam completed certain pre-clinical studies and the Phase 1 clinical study, with The Medicines Company leading and funding the development of PCSK9si from Phase 2 forward as well as potential commercialization.
Hypercholesterolemia is a condition characterized by very high levels of cholesterol in the blood which is known to increase the risk of coronary artery disease, the leading cause of death in the U.S. Some forms of hypercholesterolemia can be treated through dietary restrictions, lifestyle modifications (e.g., exercise and smoking cessation) and medicines such as statins. However, a large proportion of patients with hypercholesterolemia are not achieving adequate LDL-C levels with currently available therapies such as statins, including genetic familial hypercholesterolemia (FH) patients, acute coronary syndrome patients, high-risk patient populations (e.g., patients with coronary artery disease, diabetes, symptomatic carotid artery disease, etc.) and other patients that are statin intolerant. Severe forms of hypercholesterolemia are estimated to affect more than 500,000 patients worldwide, and as a result, there is a significant need for novel therapeutics to treat patients with hypercholesterolemia whose disease is inadequately managed by existing therapies.
About The Medicines Company
The Medicines Company's purpose is to save lives, alleviate suffering and contribute to the economics of healthcare by focusing on leading acute/intensive care hospitals worldwide. Its vision is to be a leading provider of solutions in three areas: serious infectious disease care, acute cardiovascular care and surgery and perioperative care. The company operates in the Americas, Europe and the Middle East, and Asia Pacific regions with global centers today in Parsippany, NJ, U.S and Zurich, Switzerland.
Statements contained in this press release about The Medicines Company 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," "hopes," 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 our product candidates, including PCSK9si, will advance in the clinical trials process on a timely basis or at all, whether physicians, patients and other key decision makers will accept clinical trial results, whether the company will make regulatory submissions for its product candidates on a timely basis or at all, whether its 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 from time to time in the Company's periodic reports and registration statements filed with the Securities and Exchange Commission including, without limitation, the risk factors detailed in the Company's quarterly report on Form 10-Q filed with the SEC on May 9, 2016 , which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.
For The Medicines Company:
Bob Laverty, 973-290-6162
Vice President, Global Communications
Krishna Gorti, M.D., 973-290-6122
Vice President, Investor Relations