Heart Attack (Myocardial Infarction)
March 18, 2013
Pfizer released results from a phase IV trial of eplerenone for acute ST-segment elevation myocardial infarction (STEMI). This randomized, double-blind study, REMINDER, enrolled 1,012 patients with acute STEMI without a history of heart failure (HF) or ejection fraction (EF) <40% and without signs of HF. Subjects received, preferably before myocardial reperfusion, eplerenone 25mg-50mg once daily or placebo, in addition to standard therapy. Treatment was initiated within the first 24 hours of symptom onset (preferably within first 12 hours). Results demonstrated a statistically significant 42.9% relative risk reduction in the primary endpoint with p<0.0001 (95% confidence interval [CI] 0.439, 0.742) in patients with acute STEMI when eplerenone was initiated within the first 24 hours of onset of symptoms. The improvement in outcome was mainly driven by a significant reduction of the BNP/NT-proBNP biomarker component at one month. An elevation of BNP/NT-proBNP after one month was observed less frequently in the eplerenone group 81 (16.0%) than in the placebo group 131 (25.9%) (adjusted HR, 0.584; 95% CI 0.441-0.773; p=0.0002). Eplerenone was well tolerated. The most frequent adverse event was hyperkalemia.
April 9, 2012
Stemedica reported results from a phase II trial evaluating ischemic tolerant mesenchymal stem cells (itMSC) following myocardial infarction (heart attack). The trial enrolled 45 subjects who had experienced an acute myocardial infarct. The subjects underwent reperfusion by stent and were divided into a treatment and a control group. The treatment group received intravenous infusion of itMSCs on day seven; the control group received normal saline. The goal was to demonstrate an improvement in the pumping function of the left ventricle. At the end of three months, those in the treatment group experienced an 11 point improvement in the ejection fraction of the left ventricle compared to the control group. This level of improvement restored the treatment group's ejection fraction to normal levels. In comparison, the control group showed a level of improvement expected with standard of care; however, the ejection fraction remained below normal. The treatment group also had statistically significant improvements in two blood markers of inflammation; levels of C-reactive protein and BNP, as well as improvement in quality of life indicators. In addition, Magnetic Resonance Imaging performed day six and day 30 showed significant decreases in lesion size.
September 10, 2007
Merck announced positive results from a phase III trial of Cordaptive for the treatment of dyslipidemia. This double-blind, randomized trial enrolled 1,613 subjects who received Cordaptive (1 gram/day), extended-release niacin alone (1 gram/day) or placebo. After four weeks, the active treatment groups doubled their respective doses to 2 grams per day for an additional 20 weeks. The co-primary endpoints were the effects of 2 grams of Cordaptive versus placebo on percent changes in LDL-cholesterol (LDL-C) across weeks 12 to 24, and the effects of 1 gram of Cordaptive versus extended-release niacin on flushing symptom severity during the first week of treatment. In the subjects who advanced to 2 grams of Cordaptive, LDL-C levels were reduced from baseline by an average of 19% (versus a reduction of 0.5% with placebo). In addition, in the subjects receiving 1 mg of Cordaptive, 69% reported either no flushing symptoms or mild flushing symptoms during the first week of treatment compared to 44% of those who received extended-release niacin alone. Secondary endpoints included the effects of 2 grams of Cordaptive versus placebo on HDL-cholesterol (HDL- C) levels, triglyceride levels and other lipid parameters, and the flushing frequency and intensity of 2 grams of Cordaptive compared to extended-release niacin alone. In the subjects receiving Cordaptive 2 mg their HDL-C levels increased by an average of 19% (versus a reduction of 1.2% with placebo), and their triglyceride levels were reduced by an average of 22% (versus an increase of 3.6% with placebo). By week 24, the frequency of moderate or greater flushing was 2 days/week for subjects receiving 2 grams of Cordaptive or a placebo versus 7 days/week among those treated with 2 grams of extended-release niacin. A NDA for Cordaptive in the treatment of dyslipidemia is currently under review by the FDA.
Novartis reported positive results from a phase II trial of SPP100 for the treatment of heart failure. This trial, dubbed ALOFT (ALiskiren Observation of Heart Failure Treatment), enrolled 302 subjects who were treated with SPP100 150 mg once per day plus standard heart failure therapy or placebo plus standard therapy. Results revealed that subjects treated with SPP100 plus standard therapy showed significant reductions in B-type natriuretic peptide (BNP) which were nearly five times greater than reductions with standard therapy alone (-61 pg/mL versus -12 pg/mL, p= 0.016). Treatment with SPP100 was safe and well tolerated, with a profile similar to placebo. Based on the results, Novartis plans to proceed with the development of SPP100 into phase III trials.
Sanofi-Aventis issued positive long-term results from two clinical trials of Lovenox for the treatment of acute ST-segment elevation myocardial infarction (STEMI). The first trial, dubbed ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment, Thrombolysis in Myocardial Infarction -- Study 25), enrolled 4,676 subjects. The subjects received adjunctive anticoagulation therapy with either Lovenox or unfractionated heparin (UFH) in a blinded fashion during fibrinolysis and underwent subsequent percutaneous coronary intervention (PCI). Results at one year showed that the primary endpoint of death or nonfatal myocardial infarction remained significantly in favor or Lovenox versus UFH (15.8% versus 17.0%, p-0.01). Net clinical benefit, including all cause of death, nonfatal myocardial infarction and nonfatal disabling stroke, was also significantly in favor of Lovenox when compared to UFH through one year (16.0% versus 17.3%, p=0.007). The second trial, dubbed STEEPLE (Safety and Efficacy of Enoxaparin in Percutaneous Coronary Intervention (PCI): An International Randomized Evaluation), enrolled 3,528 subjects. The trial was designed to evaluate a single intravenous dose of Lovenox (0.5 mg/kg and 0.75 mg/kg) versus Activated Clotting Time (ACT)-adjusted intravenous UFH in subjects undergoing non-emergency PCI. The primary endpoint was the incidence of major and minor bleeding. Results at one year showed that the composite of all cause death at 1 year and major bleeding was 3.1% for Lovenox 0.5 mg/kg (p=0.06 vs. UFH), 3.4% for Lovenox 0.75 mg/kg (p=0.07 vs. UFH), 3.3% for the two Lovenox arms combined (p=0.03 vs. UFH) and 4.7% for UFH. Lovenox has been approved for the treatment of acute coronary syndromes.
November 28, 2005
AstraZeneca reported positive results of their phase IIb DISPERSE2 trial of AZD6140, their investigational platelet-aggregation inhibitor for the treatment of acute coronary syndromes (ACS). Primary safety data indicated comparable rates of bleeding events for low- and high-dose treatment groups and a control group receiving the approved drug clopidogrel at the end of the treatment period: 10.2% of subjects in each of the two treatment groups experienced bleeds of any severity, vs. 9.2% for the approved drug. Incidence of major bleed events were 7.8% and 6.2% for low- and high-dose AZD6140 groups respectively, vs. 8.0% for the approved drug. Finally, data from an interim 4-week analysis indicated all-severity bleed rates of 9.6%, 7.7% and 8.0%, respectively. This double-blind, parallel group, randomized, dose-ranging study enrolled 990 ACS patients, who received one of two doses of AZD6140 (90 or 180 mg, twice daily) or a standard dose of clopidogrel (75 mg once daily) for 12 weeks.
Corgentech announced negative results of a phase III trial, dubbed PREVENT IV, of edifoligide for the prevention of graft failure in coronary artery bypass graft (CABG) surgery. Trial data failed to significantly reduce the number of patients with one or more grafts at least 75% blocked at 1 year, the trial’s primary endpoint: 45.2% of patients who received the drug had 75% blockage, compared to 46.3% for the control group. Further, no difference was noted in the total number of 75%-occluded graft veins between edifoligide (28.5% of grafts) and control. (29.7% of grafts) groups. This randomized, double-blind, placebo-controlled trial enrolled 3,014 CABG patients across 107 US sites, each of whom had received at least two venous grafts. Further development of edifoligide for this indication was not planned.
November 14, 2005
Osiris Therapeutics has reported positive preliminary results of a phase I trial of their Provacel adult mesenchymal stem cell therapy, under investigation for the treatment of heart attack. Interim safety data from the study indicated a positive overall profile, with incidence of serious and overall treatment-related adverse events in line with values previously determined as acceptable. This ongoing safety and preliminary efficacy trial enrolled patients with congestive heart failure suffering from their first heart attack. Based on these results, the trial's independent Data Safety Monitoring Board recommended continuation of the study and initiation of a higher-dose treatment regimen.
May 2, 2005
Cardiome Pharma announced positive results of a phase Ib trial of a controlled-release oral formulation of RSD1235, for the maintenance of normal heart rhythm following atrial fibrillation (AF). The company is also investigating an intravenous formulation of the drug, for the acute treatment of AF, which is currently in phase III development. Trial data yielded stable pharmacokinetics and a positive tolerability profile both following post-meal and fasting administration to both normal and slow drug metabolizers. This open-label study enrolled healthy volunteers, and was designed to investigate the safety, tolerability, pharmacokinetics, and optimum dosing regimen of the drug in patients with varying drug metabolism rates and food intake. The company announced plans to initiate a phase II trials of the drug during the second half of 2005.
October 25, 2004
deCODE genetics issued positive preliminary results of a phase IIa trial of DG031, their investigational cardioprotective for the prevention of heart attack. Trial data met their primary efficacy endpoint, demonstrating a significant reduction in one or more biomarkers of heart attack, in at-risk patients. This included a significant reduction of leukotriene B4 at all investigational doses, and significant reductions of MPO and sICAM-I at the highest investigational dose, compared with placebo. No serious tolerability concerns were raised, though one myocardial infarction occurred in the active drug group and one sudden death occurred in a subject receiving placebo. This double-blind, placebo-controlled, dose-escalating crossover study enrolled 172 subjects with a history or a genetic predisposition to heart attack.
Liponex has issued preliminary results from a phase I trial of CRD5, for the treatment hypercholesterolemia and atherosclerosis. Data from the trial showed that drug was safe and well tolerated with no adverse reactions reported, meeting their primary endpoint. In addition, secondary efficacy data indicated that the drug showed significant efficacy in both increasing HDL (good) cholesterol (18% over baseline) and reducing LDL (bad) cholesterol (15%-60% from baseline). This open-label study enrolled 56 healthy volunteers, who received CRD5 for two weeks. Based upon these results, Liponex announced plans to initiate phase II trials of CRD5 in 2005.
Vertex Pharmaceuticals reported preliminary results from a phase IIa trial of VX-702, their investigational p38 MAP kinase inhibitor, for the treatment of acute coronary syndrome in patients undergoing percutaneous coronary intervention. Study results indicate that the drug met its primary safety and pharmacokinetic endpoints, with no significant increase in adverse events compared with placebo, and no significant difference in incidence of liver enzyme abnormalities. The drug also met its secondary efficacy endpoints, significantly reducing serum C-reactive protein (CRP) levels up to 48 hours after treatment in all dosing cohorts compared with placebo. This double-blind, placebo-controlled dose escalation study enrolled a total of 45 patients with unstable angina and acute coronary syndrome. Subjects were randomized to receive one of four doses of the drug or placebo once daily for five days, prior to PCI intervention.
September 27, 2004
Avant Immunotherapeutics has published the results from a phase II trial of their cardioprotective investigational drug TP10 in the journal Circulation. The trial did not meet its primary endpoint, a significant decrease in mortality or acute myocardial infarction following cardiopulmonary bypass (CPB) during cardiac surgery. However, when data were analyzed for male patients only, the drug was successful in both outcomes, reducing mortality by 36% in all men and by 43% in CABG men. The drug did demonstrate significant pharmacodynamic activity on its target in both men and women. This multi-center, double-blind, placebo-controlled study enrolled a total of 564 high risk men and women undergoing cardiac surgery including CPB. Avant announced that it plans to initiate a second, all-female phase II trial, in addition to phase III testing.
Medicure has announced positive results from a phase I trial of a new IV formulation of their lead compound MC-1, for the treatment of cardiovascular emergencies, including stroke and acute coronary syndrome. The drug was found to be safe and well tolerated in healthy volunteers, and, similar to the effect observed with the drug’s oral formulation, did not produce any significant adverse cardiovascular effects, a common concern with other similar products. This trial and the IV formulation of the drug were designed to expand the clinical potential of MC-1, and permit use of the drug both pre-operatively, as a cardioprotective, and as an intervention therapy in acute cardiovascular events.
December 2, 2002
Alexion Pharmaceuticals reported mixed results from two phase II trials investigating pexelizumab, an antibody fragment for the treatment of acute myocardial infarction (AMI). The first study, designed to evaluate the possible benefits of pexelizumab in acute myocardial infarction subjects who underwent primary percutaneous transluminal coronary angioplasty did not reach its primary endpoint of infarct size reduction. However, pexelizumab was associated with a statistically significant 70% reduction in 90 day mortality (placebo 5.9% vs. pexelizumab 1.8%), a secondary endpoint. The double blind, randomized study enrolled 814 AMI patients who had received angioplasty. The second study, designed to evaluate the possible benefits of pexelizumab in subjects who sustained an AMI and were treated with a thrombolytic did not reach its primary endpoint of reduction in infarct size. There was no reduction in mortality, but subjects outside the U.S. had greater cardiac damage at baseline and lower utilization of revascularization procedures after study entry. The trial, a double blind, randomized, multinational study enrolled 920 subjects with acute myocardial infarction who had received thrombolytics. Pexelizumab appeared to be well tolerated in both studies with the most common adverse events being headache, chest pain, hypotension, and ventricular tachycardia.
Vasogen reported positive results from a phase II trial investigating their immune modulation therapy (IMT) for the treatment of cardiovascular and other inflammatory diseases. The double blind, placebo-controlled trial demonstrated a significant reduction in the risk of death and hospitalization, improvements in a clinical composite score, and improvements in key electrocardiogram (ECG) measures among CHF patients receiving IMT. There was also a significant reduction in the risk of death (1 vs. 7 deaths) and hospitalization (12 vs. 21 hospitalizations), versus placebo. Data also showed that IMT improved key ECG measures (QTc interval and QT dispersion) and that these electrophysiological effects were consistent with the observed positive impact on mortality.
February 25, 2002
Avant Immunotherapeutics reported that TP10 failed to meet the primary endpoint in a double-blind, placebo-controlled phase II trial. The trial included 564 adult subjects undergoing high-risk cardiac surgery. Subjects were randomized to receive either a placebo or one of four doses of TP10 as a 30-minute intravenous infusion, and they were followed for 28 days post-surgery. The primary endpoint was the comparison of TP10- and placebo-treated subjects who experienced either death, myocardial infarction, required prolonged intubation or prolonged intra-arterial balloon pump therapy. The results did not show any clinically important differences between the placebo and four dose groups.