NEW ORLEANS, Nov. 6 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. announced results of the PROTECT trial, which was designed to compare the glycoprotein (GP) IIb-IIIa inhibitor INTEGRILIN with the direct thrombin inhibitor bivalirudin in high risk patients using clinical and physiologic endpoints. On the physiologic primary endpoint of coronary flow reserve (CFR), a measure of coronary artery flow, adjusted as pre-specified, the primary endpoint favored bivalirudin but was not statistically significant when imputed as pre-specified for abrupt closure, no reflow, and thrombotic bail-out during percutaneous coronary intervention (PCI) (p=0.036 by intent-to-treat; p=0.13 imputed, 1.43 bivalirudin versus 1.33 pooled INTEGRILIN, respectively). However, INTEGRILIN showed a statistically significant (p=0.048, adjusted for baseline as pre-specified) improvement in myocardial perfusion (a measure of blood flow to the heart muscle) compared to bivalirudin. Myocardial perfusion has been shown to correlate highly with improved survival.(1)
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"A key finding from this study is that better cardiac blood flow resulted in better clinical outcomes. While the overwhelming majority of patients (over 93%) left the cath lab with normal flow in the artery, INTEGRILIN significantly improved flow downstream into the heart muscle itself, as measured by TIMI Myocardial Perfusion Grade (TMPG)," said C. Michael Gibson, MS, MD, principal investigator in the PROTECT study and Associate Chief of Cardiology in the Cardiovascular Division of Beth Israel Hospital at Harvard Medical School. "This study adds to the growing body of scientific literature linking improved blood flow into the heart muscle with improved clinical outcomes. Further, this study highlights the importance of arriving to the cath lab with good flow to the muscle."
Previous studies have shown up to a seven-fold increase in 30-day mortality following heart attack in patients whose flow in the artery was normal but whose myocardial perfusion was rated TMPG 0 or 1, versus those who demonstrated normal TMPG 3.(2) TMPG measurement shows how effectively blood flow is restored to the heart muscle following therapeutic and mechanical intervention. In the PROTECT study, when compared to those acute coronary syndrome (ACS) patients who received bivalirudin, 13.8% more INTEGRILIN- treated patients achieved normal perfusion TMPG 3, a statistically significant benefit (p=0.048 adjusted for baseline as pre-specified).
In addition, in the PROTECT study, other endpoints showed that among patients with ischemia, INTEGRILIN(R) (eptifibatide) Injection showed a statistically significant reduction in median duration of ischemia in the first 24 hours post-PCI versus bivalirudin (36 minutes versus 169 minutes, p=0.013). Furthermore, measurement of troponin and CK-MB, important protein and enzymatic markers of cardiac damage, directionally showed lower peak rises among those patients who received INTEGRILIN. In the subset of the highest risk ACS patients, those with inadequate blood flow to the heart muscle upon arrival in the catheterization lab (TMPG 0, 1 or 2), high troponin levels at baseline correlated significantly with impaired blood flow. Post-PCI, patients who received INTEGRILIN in this sub-group had a significantly lower elevation in troponin and CK-MB post-PCI versus those who received bivalirudin (3.5 vs. 5.3, p=0.04, 2.7 vs. 10, p=0.009, respectively), signifying a possible reduction in heart muscle damage with use of INTEGRILIN.
Across all patient groups, only 18 of the 857 patients (2%), experienced any TIMI major or minor bleeding event. In the major safety endpoint for the trial there was no reported TIMI major bleeding in the INTEGRILIN arm with UFH or in the bivalirudin arm. There was a 1.5% incidence of TIMI major bleeding in the INTEGRILIN arm with enoxaparin. TIMI minor bleeding was 2.5% in the pooled INTEGRILIN arms compared to 0.4% in the bivalirudin arm (p=0.027).
"All clinical efficacy outcome measures in this trial favored INTEGRILIN over bivalirudin," said Nancy Simonian, MD, senior vice president, clinical development at Millennium Pharmaceuticals, Inc. "This study reinforces the need for early and aggressive use of INTEGRILIN in ACS patients to preserve the heart muscle and protect against future cardiac events."
About PROTECT
(Randomized Trial to Evaluate the Relative PROTECTion Against Post-PCI Microvascular Dysfunction and Post-PCI Ischemia Among Anti-Platelet and Anti-Thrombotic Agents) PROTECT was a multi-center, open-label, randomized trial involving 857 high-risk patients in over 100 sites in North America. The primary objective of the PROTECT-TIMI 30 trial was to compare the efficacy and safety of the glycoprotein IIb-IIIa inhibitor INTEGRILIN (with either unfractionated heparin, UFH, or enoxaparin) to the direct thrombin inhibitor, bivalirudin alone in patients undergoing PCI with unstable angina (UA) or non- ST-segment elevation myocardial infarction (NSTEMI), also known as acute coronary syndromes (ACS). These agents were assessed for efficacy in the trial by examining the delivery of blood flow both through the artery, as measured by coronary flow reserve (CFR), and directly to the heart muscle, as measured by TIMI myocardial perfusion grade (TMPG), as well as for safety measured by bleeding events.
PROTECT results were announced during the Texas Heart Institute Symposium on Saturday, November 6, in conjunction with the American Heart Association Scientific Sessions Symposium 2004. This event is not part of the official Scientific Sessions 2004 as planned by the AHA Committee on Scientific Sessions Program.
About INTEGRILIN(R) (eptifibatide) Injection
INTEGRILIN is indicated for the treatment of patients with acute coronary syndrome (unstable angina/non-ST-segment myocardial infarction), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (PCI). It is also indicated in the United States for the treatment of patients at time of PCI, including in patients undergoing intracoronary stenting.
INTEGRILIN is contraindicated in patients with a history of bleeding diathesis, or evidence of abnormal bleeding within the previous 30 days; severe hypertension (systolic blood pressure greater than 200 mm Hg or diastolic blood pressure greater than 110 mm Hg) not adequately controlled on antihypertensive therapy; major surgery within the preceding six weeks; history of stroke within 30 days, or any history of hemorrhagic stroke; current or planned administration of another parenteral GP IIb-IIIa inhibitor; dependency on renal dialysis; or known hypersensitivity to any component of the product.
Bleeding is the most common complication encountered during INTEGRILIN therapy. In the registration trials, the majority of excess major bleeding events were localized at the femoral artery access site. Oropharyngeal, genitourinary, gastrointestinal and retroperitoneal bleeding were also seen more commonly with INTEGRILIN compared to placebo.
For inquiries about INTEGRILIN, patients and physicians can call 1-(888)-267-4MED.
INTEGRILIN is co-promoted and co-developed by Millennium Pharmaceuticals, Inc. and Schering-Plough Corporation in the U.S.
About The Company
Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE(R) (bortezomib) for Injection, a novel cancer product, co-promotes INTEGRILIN(R) (eptifibatide) Injection, a market-leading cardiovascular product, and has a robust clinical development pipeline of product candidates. The Company's research, development and commercialization activities are focused in three therapeutic areas: oncology, cardiovascular, and inflammation. By applying its knowledge of the human genome, its understanding of disease mechanisms, and its industrialized drug discovery platform, the Company is seeking to develop breakthrough products.
This press release contains "forward-looking statements," including statements about the Company's growth and discovery and development of products. Various important risks may cause the Company's actual results to differ materially from the results indicated by these forward-looking statements, including: adverse results in its drug discovery and clinical development programs; failure to obtain patent protection for its discoveries; commercial limitations imposed by patents owned or controlled by third parties; the Company's dependence upon strategic alliance partners to develop and commercialize products and services based on the Company's work; difficulties or delays in obtaining regulatory approvals to market products and services resulting from the Company's development efforts; product withdrawals; competitive factors; difficulties or delays in manufacturing the Company's products; government and third party reimbursement rates; the commercial success of INTEGRILIN(R) (eptifibatide) Injection; achieving revenue consistent with internal forecasts; and the requirement for substantial funding to conduct research and development and to expand commercialization activities. For a further list and description of the risks and uncertainties the Company faces, see the reports it has filed with the Securities and Exchange Commission. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
(1) Gibson et.al. Circulation 2000;101:125-130 (2) Gibson et.al. Circulation 2004;109:3096-3105 Contacts: Lisa Adler (media) (617) 444-3285 Gina Price Nugent (investor) (617) 551-3611
Photo: http://www.newscom.com/cgi-bin/prnh/19991220/MLNMLOGO Millennium Pharmaceuticals, Inc.
(Logo: http://www.newscom.com/cgi-bin/prnh/19991220/MLNMLOGO )
"A key finding from this study is that better cardiac blood flow resulted in better clinical outcomes. While the overwhelming majority of patients (over 93%) left the cath lab with normal flow in the artery, INTEGRILIN significantly improved flow downstream into the heart muscle itself, as measured by TIMI Myocardial Perfusion Grade (TMPG)," said C. Michael Gibson, MS, MD, principal investigator in the PROTECT study and Associate Chief of Cardiology in the Cardiovascular Division of Beth Israel Hospital at Harvard Medical School. "This study adds to the growing body of scientific literature linking improved blood flow into the heart muscle with improved clinical outcomes. Further, this study highlights the importance of arriving to the cath lab with good flow to the muscle."
Previous studies have shown up to a seven-fold increase in 30-day mortality following heart attack in patients whose flow in the artery was normal but whose myocardial perfusion was rated TMPG 0 or 1, versus those who demonstrated normal TMPG 3.(2) TMPG measurement shows how effectively blood flow is restored to the heart muscle following therapeutic and mechanical intervention. In the PROTECT study, when compared to those acute coronary syndrome (ACS) patients who received bivalirudin, 13.8% more INTEGRILIN- treated patients achieved normal perfusion TMPG 3, a statistically significant benefit (p=0.048 adjusted for baseline as pre-specified).
In addition, in the PROTECT study, other endpoints showed that among patients with ischemia, INTEGRILIN(R) (eptifibatide) Injection showed a statistically significant reduction in median duration of ischemia in the first 24 hours post-PCI versus bivalirudin (36 minutes versus 169 minutes, p=0.013). Furthermore, measurement of troponin and CK-MB, important protein and enzymatic markers of cardiac damage, directionally showed lower peak rises among those patients who received INTEGRILIN. In the subset of the highest risk ACS patients, those with inadequate blood flow to the heart muscle upon arrival in the catheterization lab (TMPG 0, 1 or 2), high troponin levels at baseline correlated significantly with impaired blood flow. Post-PCI, patients who received INTEGRILIN in this sub-group had a significantly lower elevation in troponin and CK-MB post-PCI versus those who received bivalirudin (3.5 vs. 5.3, p=0.04, 2.7 vs. 10, p=0.009, respectively), signifying a possible reduction in heart muscle damage with use of INTEGRILIN.
Across all patient groups, only 18 of the 857 patients (2%), experienced any TIMI major or minor bleeding event. In the major safety endpoint for the trial there was no reported TIMI major bleeding in the INTEGRILIN arm with UFH or in the bivalirudin arm. There was a 1.5% incidence of TIMI major bleeding in the INTEGRILIN arm with enoxaparin. TIMI minor bleeding was 2.5% in the pooled INTEGRILIN arms compared to 0.4% in the bivalirudin arm (p=0.027).
"All clinical efficacy outcome measures in this trial favored INTEGRILIN over bivalirudin," said Nancy Simonian, MD, senior vice president, clinical development at Millennium Pharmaceuticals, Inc. "This study reinforces the need for early and aggressive use of INTEGRILIN in ACS patients to preserve the heart muscle and protect against future cardiac events."
About PROTECT
(Randomized Trial to Evaluate the Relative PROTECTion Against Post-PCI Microvascular Dysfunction and Post-PCI Ischemia Among Anti-Platelet and Anti-Thrombotic Agents) PROTECT was a multi-center, open-label, randomized trial involving 857 high-risk patients in over 100 sites in North America. The primary objective of the PROTECT-TIMI 30 trial was to compare the efficacy and safety of the glycoprotein IIb-IIIa inhibitor INTEGRILIN (with either unfractionated heparin, UFH, or enoxaparin) to the direct thrombin inhibitor, bivalirudin alone in patients undergoing PCI with unstable angina (UA) or non- ST-segment elevation myocardial infarction (NSTEMI), also known as acute coronary syndromes (ACS). These agents were assessed for efficacy in the trial by examining the delivery of blood flow both through the artery, as measured by coronary flow reserve (CFR), and directly to the heart muscle, as measured by TIMI myocardial perfusion grade (TMPG), as well as for safety measured by bleeding events.
PROTECT results were announced during the Texas Heart Institute Symposium on Saturday, November 6, in conjunction with the American Heart Association Scientific Sessions Symposium 2004. This event is not part of the official Scientific Sessions 2004 as planned by the AHA Committee on Scientific Sessions Program.
About INTEGRILIN(R) (eptifibatide) Injection
INTEGRILIN is indicated for the treatment of patients with acute coronary syndrome (unstable angina/non-ST-segment myocardial infarction), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (PCI). It is also indicated in the United States for the treatment of patients at time of PCI, including in patients undergoing intracoronary stenting.
INTEGRILIN is contraindicated in patients with a history of bleeding diathesis, or evidence of abnormal bleeding within the previous 30 days; severe hypertension (systolic blood pressure greater than 200 mm Hg or diastolic blood pressure greater than 110 mm Hg) not adequately controlled on antihypertensive therapy; major surgery within the preceding six weeks; history of stroke within 30 days, or any history of hemorrhagic stroke; current or planned administration of another parenteral GP IIb-IIIa inhibitor; dependency on renal dialysis; or known hypersensitivity to any component of the product.
Bleeding is the most common complication encountered during INTEGRILIN therapy. In the registration trials, the majority of excess major bleeding events were localized at the femoral artery access site. Oropharyngeal, genitourinary, gastrointestinal and retroperitoneal bleeding were also seen more commonly with INTEGRILIN compared to placebo.
For inquiries about INTEGRILIN, patients and physicians can call 1-(888)-267-4MED.
INTEGRILIN is co-promoted and co-developed by Millennium Pharmaceuticals, Inc. and Schering-Plough Corporation in the U.S.
About The Company
Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE(R) (bortezomib) for Injection, a novel cancer product, co-promotes INTEGRILIN(R) (eptifibatide) Injection, a market-leading cardiovascular product, and has a robust clinical development pipeline of product candidates. The Company's research, development and commercialization activities are focused in three therapeutic areas: oncology, cardiovascular, and inflammation. By applying its knowledge of the human genome, its understanding of disease mechanisms, and its industrialized drug discovery platform, the Company is seeking to develop breakthrough products.
This press release contains "forward-looking statements," including statements about the Company's growth and discovery and development of products. Various important risks may cause the Company's actual results to differ materially from the results indicated by these forward-looking statements, including: adverse results in its drug discovery and clinical development programs; failure to obtain patent protection for its discoveries; commercial limitations imposed by patents owned or controlled by third parties; the Company's dependence upon strategic alliance partners to develop and commercialize products and services based on the Company's work; difficulties or delays in obtaining regulatory approvals to market products and services resulting from the Company's development efforts; product withdrawals; competitive factors; difficulties or delays in manufacturing the Company's products; government and third party reimbursement rates; the commercial success of INTEGRILIN(R) (eptifibatide) Injection; achieving revenue consistent with internal forecasts; and the requirement for substantial funding to conduct research and development and to expand commercialization activities. For a further list and description of the risks and uncertainties the Company faces, see the reports it has filed with the Securities and Exchange Commission. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
(1) Gibson et.al. Circulation 2000;101:125-130 (2) Gibson et.al. Circulation 2004;109:3096-3105 Contacts: Lisa Adler (media) (617) 444-3285 Gina Price Nugent (investor) (617) 551-3611
Photo: http://www.newscom.com/cgi-bin/prnh/19991220/MLNMLOGO Millennium Pharmaceuticals, Inc.
© 2004 PR Newswire
