Interim Analyses Indicate CHAMPION Program Will Not Meet Efficacy Endpoints
Company to Continue and Accelerate Phase 2/3 Studies of Cangrelor in Settings Where Oral Drugs Cannot Be Used or Short Half-Life Is Desirable
The Medicines Company (NASDAQ: MDCO) today announced that it is discontinuing its Phase 3 CHAMPION clinical trial program of cangrelor in patients undergoing percutaneous coronary intervention (PCI).
The program's independent Interim Analysis Review Committee (IARC), after conferring with the Drug Safety Monitoring Board, reported to the Company that the CHAMPION-PLATFORM trial would not meet the goal of demonstrating persuasive evidence of clinical effectiveness that could form the basis for regulatory approval. This placebo-controlled trial compared treatment with cangrelor (in combination with usual care) to usual care in patients who require PCI.
The IARC also reported to the Company that, based on updated information, the CHAMPION-PCI trial, a clinical trial comparing treatment with cangrelor to clopidogrel (600 mg loading dose) in patients who require PCI, showed no significant differences in measures of clinical effectiveness.
Safety findings for the program were consistent with those expected from short-term P2Y12 platelet inhibition and included an increase in minor bleeding among patients given cangrelor in comparison to placebo, but not in comparison to clopidogrel.
Based on the totality of these data, the IARC has recommended that enrollment in both trials be discontinued and that all remaining data should be collected and analyzed. The Company is in the process of notifying the investigators and regulatory agencies of the discontinuation of the CHAMPION program.
The IARC also recommended that the Company should consider focusing on short-term use of cangrelor in settings where oral drugs cannot be used or when a short half-life is highly desirable. Consistent with guidance from the IARC, cangrelor is already being studied in such a setting. The BRIDGE study aims to establish the dosage of cangrelor that achieves greater than or equal to 60% inhibition of platelet aggregation for five days. The Company plans to enroll approximately 200 patients who discontinue clopidogrel in preparation for cardiac surgery. The aim is to show safe "bridging" of patients during the pre- and post-surgical period of risk. If successful, this approach may form the basis for subsequent regulatory filings.
"We are disappointed that the CHAMPION program has not provided sufficient evidence of the clinical effectiveness of cangrelor to warrant completion of these Phase 3 trials. We thank the Investigators and oversight Committees for their work and we will follow their guidance. The trials are being discontinued; we plan to finalize data collection and analyses, and we expect that the data will be presented at a major cardiology meeting in due course. We will now move forward more quickly with our studies where cangrelor is tested to enable safe 'bridging' of patients undergoing surgery. In this setting of high unmet medical need, long-term clopidogrel is often discontinued at considerable risk to patients. The rapid onset, offset and titratable anti-platelet pharmacology of cangrelor seems ideally suited for this potential use. The development of cangrelor will therefore continue," said Clive Meanwell, M.D., Ph.D., Chief Executive Officer of The Medicines Company.
"Looking longer term, it is important to note that The Medicines Company is not dependent on a single product. We have a diversified portfolio of current and pipeline products, industry-leading operational capabilities and we are cash flow positive. We believe the Company is well positioned to deliver future growth and long-term shareholder value. We remain committed to our strategy of building a leading global critical care hospital medicines business. We will continue to focus on our market-leading Angiomax product, the Angiox business, the ongoing Cleviprex launch in the United States and international Cleviprex regulatory filings now underway, advancing Phase 3 trials of oritavancin and on our early stage development program with CU2010," he continued.
The Company noted that the discontinuation of the CHAMPION program will result in cost savings of approximately $5 million in 2009.
Cangrelor
Cangrelor is an investigational intravenous antiplatelet agent exclusively licensed in December 2003 from AstraZeneca.
The Phase 3 program for cangrelor consisted of two large studies with a combined planned total enrollment of 15,400 patients. The CHAMPION-PCI study, which commenced enrollment in March 2006, enrolled 98% of the patients out of a planned target of 9,000 patients. The objective of this study was to demonstrate that the efficacy of cangrelor is superior, or at least non-inferior, to that of clopidogrel in subjects requiring PCI as measured by a composite of all-cause mortality, myocardial infarction (MI), and ischemia driven revascularization (IDR) at 48 hours after PCI. The second trial in the Phase 3 program, referred to as CHAMPION-PLATFORM, commenced enrollment in October 2006 and enrolled 83% of the planned target of 6,400 patients. The objective of this study was to demonstrate that the efficacy of cangrelor (combined with usual care) is superior to that of usual care, in subjects requiring PCI, as measured by a composite of all-cause mortality, MI, and IDR.
In both studies, the incidence of hemorrhage by clinically relevant criteria (ACUITY, GUSTO, TIMI) and the need for blood transfusions was also measured up to 48 hours.
The Medicines Company will host a conference call today, Wednesday, May 13, 2009 at 8:30 a.m. Eastern Time. The conference call will be available via phone and webcast. The dial in information is listed below:
Domestic Dial In: 866-383-8108 International Dial In: 617-597-5343 Passcode for both dial in numbers: 97511198 Replay is available from 11:30 a.m. Eastern Time following the conference call through May 27, 2009. To hear a replay of the call, dial 888-286-8010 (domestic) and 617-801-6888 (international). Passcode for both dial in numbers is 27752004. This call is being webcast and can be accessed at The Medicines Company website at www.themedicinescompany.com. About The Medicines Company The Medicines Company (NASDAQ: MDCO) is focused on advancing the treatment of critical care patients through the delivery of innovative, cost-effective medicines to the worldwide hospital marketplace. The Company markets Angiomax® (bivalirudin) in the United States and other countries for use in patients undergoing coronary angioplasty, and Cleviprex® (clevidipine butyrate) injectable emulsion in the United States for the reduction of blood pressure when oral therapy is not feasible or not desirable. The Company also has an investigational antiplatelet agent, cangrelor, in late-stage development and a serine protease inhibitor, CU-2010, in early-stage development. Through the acquisition of Targanta Therapeutics, The Medicines Company's pipeline includes oritavancin, a semi-synthetic lipoglycopeptide antibiotic currently awaiting EU regulatory approval. The Medicines Company's website is www.themedicinescompany.com. Cautionary Note Regarding Forward-Looking Statements 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 "estimates" 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 Company will be able to obtain regulatory approvals; whether the Company's products and product candidates will advance in the clinical trial process on a timely basis or at all; whether clinical trial results will warrant submission of applications for regulatory approval; whether physicians, patients and other key decision-makers will accept clinical trial results; whether the Company will be able to successfully distribute and market its approved products; 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 on May 11, 2009, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements. Contact: Katherine Stueland WeissComm Partners Phone: (312) 646-6299 kstueland@wcpglobal.com Robyn Brown The Medicines Company Phone: (973) 290-6000 investor.relations@themedco.com