The Medicines Company Announces Positive Top-Line Results from Day 90 Interim Analysis in Ongoing ORION-1 Phase 2 Study of PCSK9si
The Medicines Company (NASDAQ:MDCO) today announced top-line results from the interim analysis with Day 90 follow-up for all 501 patients enrolled in the ongoing ORION-1 study of PCSK9si, its investigational first-in-class PCSK9 synthesis inhibitor. Data from the interim analysis confirm the significant and durable LDL-C reduction demonstrated up to Day 90 in the preceding Phase 1 study. PCSK9si was well tolerated and no material safety issue was observed in the Day 90 interim analysis of unblinded safety data, including no investigational drug-related elevation of liver enzymes, neuropathy or change in renal function. Injection site reactions were infrequent, mild or moderate, and short-lived.
“We are highly encouraged by the strength and consistency of the Day 90 efficacy and safety data from ORION-1, which build significantly on the promise generated by the preceding Phase 1 study of PCSK9si,” said Clive Meanwell, M.D., Ph.D., Chief Executive Officer of The Medicines Company. “These compelling interim data affirm PCSK9si’s highly-competitive profile and validate PCSK9si’s game-changing potential. We look forward to presenting results from the ORION-1 study, including Day 180 follow-up for up to 200 patients, at the AHA meeting on November 15, 2016.”
David Kallend, MBBS, Vice President and Global Medical Director at The Medicines Company, added, “Based on the results from our ORION-1 Day 90 interim analysis, PCSK9si has again demonstrated robust and durable knockdown of LDL-C, as well as impressive safety and tolerability. These results validate a triannual, and potentially biannual, low volume subcutaneous dose regimen, which we believe represents a compelling, highly-differentiated approach for treating patients with hypercholesterolemia.”
“The thoughtful and robust design of the ORION-1 study has delivered highly impressive interim data,” said John J.P. Kastelein, M.D., Ph.D., Professor of Medicine and Chairman of the Department of Vascular Medicine at the Academic Medical Center of the University of Amsterdam. “The potential for management of hypercholesterolemia with two or three low volume injections per year could open a new, transformative and affordable pathway for patients and physicians in the treatment of atherosclerotic cardiovascular disease.”
The interim analysis of Day 90 follow-up for all 501 patients, as well as top-line data from Day 180 follow-up for up to 200 patients, will be presented in a Late-Breaking Clinical Trials session at the AHA Scientific Sessions 2016 on November 15, 2016 in New Orleans. In order to protect the scientific integrity of the ongoing ORION-1 study, the Company does not expect to provide additional information or make further public statements regarding the results of the study in advance of the ORION-1 presentation at the AHA Scientific Sessions. The Company anticipates that data from Day 180 follow-up in all 501 patients will be completed, analyzed and top-line results disclosed before the end of 2016.
ORION-1 is a placebo-controlled, double-blind, randomized, dose-finding Phase 2 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 trial compares the effect of different doses of PCSK9si and evaluates the potential for dosing no more than two, three or four times per year.
About PCSK9si (also known as ALN-PCSsc)
PCSK9si is an investigational proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis inhibitor, which acts via RNA interference, being developed for the treatment of hypercholesterolemia. PCSK9 is a genetically-validated protein regulator of LDL receptor metabolism. 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 inhibiting 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 or discontinuations due to adverse events.
The Medicines Company and Alnylam Pharmaceuticals are collaborating in the advancement of PCSK9si per their 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.
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 mission is to create transformational solutions to address the most pressing healthcare needs facing patients, physicians and providers in three critical therapeutic areas: serious infectious disease care, cardiovascular care and surgery and perioperative care. The Company is headquartered in Parsippany, New Jersey, with global innovation centers in California and Switzerland.
Forward Looking Statements
Statements contained in this press release 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," “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 our product candidates, including the ORION-1 study of PCSK9si, will advance in the clinical process on a timely basis, or at all, or succeed in achieving their specified endpoints; 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 Securities and Exchange Commission on August 5, 2016, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.
The Medicines Company
Meg Langan, 973-290-6319
Krishna Gorti, MD, 973-290-6122
Vice President, Investor Relations