The Medicines Company (NASDAQ:MDCO) today provided a progress update on the ongoing ORION-1 study of PCSK9si, its investigational first-in-class PCSK9 synthesis inhibitor.
ORION-1 is a placebo-controlled, double-blind, randomized Phase II trial of single or multiple subcutaneous injections of PCSK9si in 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. The study exceeded its enrollment target of 480 patients ahead of schedule, enrolling a total of 501 patients between January 21, 2016 and June 2, 2016.
An interim analysis of Day 90 follow-up for all 501 patients will be conducted and presented in the Late-Breaking Clinical Trial Session at the AHA Scientific Sessions 2016 on November 15, 2016 in New Orleans. In addition, the Company anticipates that top-line data from Day 180 follow-up for up to 200 patients will be presented at the Late-Breaking Clinical Trial Session and Day 180 follow-up in all 501 patients will be completed, analyzed and top-line results disclosed before the end of 2016.
Safety data from the ORION-1 study is subject to regular, detailed review and assessment by the Independent Data Monitoring Committee (IDMC). The IDMC has raised no safety concerns and made no safety-related study recommendations through its most recent review on August 26, 2016. Moreover, based upon the Company’s review of blinded safety data through September 29, 2016, the most recent date for which safety data has been made available, no material safety issue and, in particular, no drug-related neuropathy, elevation of liver enzymes or changes in renal function, has been observed. At that date, the 501 study patients had treatment exposure of between 4 and 8 months.
“These impressive, emerging safety data support our view that PCSK9si has a highly-competitive profile as compared with anti-PCSK antibodies and we look forward to presenting results from the ORION-1 study at the AHA meeting on November 15, 2016,” said Clive Meanwell, M.D., Ph.D., Chief Executive Officer of The Medicines Company. “In particular, we believe that PCSK9si has the unique potential to provide new, innovative solutions to patients, payers and providers through a quarterly or, potentially, bi-annual, low-volume subcutaneous dosing regime and by linking the LDL-C monitoring cycle with administration of therapy.”
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 trial 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.
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 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 I clinical study, with The Medicines Company leading and funding the development of PCSK9si from Phase II 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," “views” 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 the clinical trials for our product candidates, including the ORION-1 trial of PCSK9si, will advance in the clinical process on a timely basis or at all or succeed in achieving their specified endpoints; whether the Company is able to disclose clinical trial results on a timely basis; 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 August 5, 2016 , which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.
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Last updated on: 05/10/2016
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