The Medicines Company Provides Update on Dyslipidemia Programs
The Medicines Company (NASDAQ:MDCO) today provided an update on its clinical dyslipidemia research programs for MDCO-216 (which contains APoA-1 Milano) and PCSK9si (PCSK9 synthesis inhibitor).
MDCO-216. A planned, interim analysis of the first 40 randomized patients completing treatment in the MILANO-PILOT study of MDCO-216 has been reviewed by the Independent Data Monitoring Committee (IDM Committee). Based on the protocol and pre-defined criteria in its Charter, the IDM Committee has reported the 40-patient data to the Company in summary form and recommended that the MILANO-PILOT study continue. The pre-defined, upper statistical boundary for efficacy, which permits early termination of the study by the Company, was not met and, given the limited number of patients included in the first interim analysis, the summary data received by the Company from the IDM Committee are, at this time, inconclusive.
The Company has completed enrollment of the planned 120 patients and expects that results from the MILANO-PILOT study will be presented by its principal investigator, Dr. Steven Nissen of the Cleveland Clinic, in the Late-Breaking Clinical Trial Session at the American Heart Association (AHA) Scientific Sessions 2016 on November 15, 2016 in New Orleans.
PCSK9si. As previously disclosed, the ORION-1 Phase II trial of PCSKsi completed enrollment ahead of schedule. An interim analysis with Day 90 follow-up for all subjects 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. The Company expects that Day 180 follow-up in all subjects will be completed, analyzed and presented before the end of 2016.
“We look forward to presenting results from the MILANO-PILOT study and the ORION-1 trial at the American Heart Association meeting in New Orleans on November 15, 2016,” said Clive Meanwell, M.D., Ph.D., Chief Executive Officer of The Medicines Company. “Atherosclerotic cardiovascular disease (ACD) remains the leading cause of mortality worldwide. Our mission is to improve outcomes in ACD and drive better economics of care for patients, physicians and payers. We had hoped that the 40-patient data from the MILANO-PILOT study would meet the pre-defined efficacy threshold for early termination, but they did not and, so far, the data are inconclusive. The study is continuing and we look forward to receiving full access to the final data.”
MILANO-PILOT is a proof-of-concept, double-blind, placebo-controlled, randomized study utilizing IVUS (Intravascular Ultrasound) to measure the effect of MDCO-216 on atherosclerotic plaque burden and to evaluate MDCO-216’s impact on cholesterol efflux. The study involves 120 patients with ACS and will likewise assess the safety of weekly 20mg/kg MDCO-216 infusions over a five-week period.
MDCO-216, an investigational product not approved for commercial use in any market, is a complex of dimeric recombinant apolipoprotein A-1 Milano (ApoA-1 Milano) and a phospholipid (POPC) and is currently under development to improve cardiovascular outcomes by reducing plaque burden in patients with atherosclerotic disease. MDCO-216 mimics pre-beta HDL and induces cholesterol efflux, which is the first step in the reverse cholesterol transport, a process of removal of deposited cholesterol from vessel walls and therefore has a potential to reduce plaque burden in patients with coronary artery disease. ApoA-1 Milano is a protein discovered in residents of a Northern Italian village who remarkably have little atherosclerotic build-up despite exceptionally low levels of cardioprotective HDL in combination with elevated levels of harmful triglycerides.
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 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.
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," 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 MILANO-PILOT study of MDCO-216 and 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 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.
Matt Middleman, M.D., (212) 845-4272
The Medicines Company
Krishna Gorti, M.D., (973) 290-6122
Vice President, Investor Relations