April 2, 2007AstraZeneca reported positive results from Phase III trial,(Measuring the effects on the thickness and endothelial media: 1 OfRosuvastatin evaluation), of Crestor for the treatment of atherosclerosis. He joined the 24-month, randomized, double-blind, placebo-controlled trial 984 shows, and hypercholesterolaemic subjects with low risk of coronary artery disease andevidence of sub-clinical atherosclerosis. The results showed thatsubjects with Crestor 40 mg experienced 0.0014 mm / year and a decrease in endothelial thickness meanmaximum media carotid artery, a sign of the burden of atherosclerosis, compared to the evolution of 0.0131 mm / year for those on placebo (P ≤ 0. 0001). Inaddition, Crestor reduced demonstrated 48.8% in LDL-C and 8 1. 0% increasein HDL-C (both p ≤ placebo versus 0.0001). AstraZeneca plans to submit NDA and Crestor MAAfor in the treatment of atherosclerosis in the first half of 2007.Scios issued positive results of the second phase of the trial, dubbed FUSION II (Follow-up serial infusion of Natrecor in Advanced Heart Failure), for thetreatment of chronic decompensated heart failure (CDHF). Joined this randomized, placebo-controlled, double-blind trial of 920 subjects responded internationally.Subjects once or twice a week batches of Natrecor or placebo, and attach the optimal heart failure drugs. The primary endpoint was death and hospitalization compositeof cardiorenal at 12 weeks. The results revealed a significant difference in nostatistically primary endpoint between twogroups when added to both the optimal heart failure drugs, significantuse of devices referred to heart failure and intensive management of the disease.Basedon the results, Scios plans to push ahead with the trials in the future.November 29, 2004AtheroGenics issued mixed results from the phase IIb trial of the anti-inflammatory drug screening AGI-1067, for the treatment of atherosclerosis. Met the end point data on the effectiveness of the trial in coronary atherosclerosis, with patients receiving standard care (SC), in addition to AGI 1067, show a significant decrease in the average size of the panel a total of 3,9 MM3 (2.3%, P = 0.0015 ) after 12 months of treatment, compared with baseline. Resulted in the SC treatment and placebo, in addition to low but significant in the average size of the panel a total of 1.5 MM3 (0.8%, P = 0.45) compared with baseline, but this reduction was slightly and was large enough to make the difference between the 1067-SC Plus and AGI SC plus placebo not significant (P = 0.29). Data also met the end secondary is important, and significantly reduce the levels of myeloperoxidase, and biological markers of inflammation linked to increased risk of heart attack, and produces a significant decrease very in the total size of the board an average of 1.8 MM3 (4.8%, P <0.0001) in the sub-group of the most gravely ill patients.Joined this double-blind, placebo-controlled study total of 469 subjects, who were randomized to receive either SC plus one of three systems of AGI-1067 or placebo for 12 months.October 25, 2004Removing the genetics issued positive preliminary results of the internal phase of the trial of DG031, protective of the heart of their screening for the prevention of heart attacks. Met the end point data on the effectiveness of the trial, which shows a significant decrease in one or more biomarkers of heart attack, in patients at risk. This included a significant reduction in leukotriene B4 in each dose examination, significant reductions of MPO and sICAM I-examination in the higher dose, compared with placebo. Did not raise any serious concerns endurance, although a myocardial infarction occurred in an effective medication group and one death occurred suddenly in the subject receiving placebo. Joined this double-blind, placebo-controlled, dose escalating crossover study 172 subjects with a history or a genetic predisposition to a heart attack.Liponex released preliminary results of the first phase of the trial CRD5, to treat high cholesterol and hardening of the arteries. Data from the trial that the drug is safe and well tolerated with no adverse reactions reported, meet the primary endpoint. In addition, the data indicate that the effectiveness of secondary drug showed significant effectiveness in both increasing HDL (good) cholesterol (18% more than baseline) and the reduction of LDL (bad) cholesterol. (15% -60% of baseline) joined this open-label study, 56 healthy volunteers, who received CRD5 for two weeks. Liponex declared on the basis of these results, and plans to begin Phase II trials CRD5 in 2005.According to preliminary results of the drug vertex of the internal phase of the trial of VX-702, the examination P38 kinase inhibitor Mediterranean Action Plan, for the treatment of acute coronary syndrome in patients undergoing coronary intervention through the skin. Results of the study indicate that the drug met the primary safety end and pharmaceutical, with no significant increase in adverse events compared with placebo, and there is a significant difference in the incidence of liver enzyme abnormalities. The drug also met her end, the effectiveness of the secondary, and a significant reduction in serum C-reactive protein (CRP) levels up to 48 hours after treatment in all dose cohorts compared with placebo.Joined this double-blind, dose escalation, placebo-controlled study, a total of 45 patients with unstable angina and acute coronary syndrome. The selection of a group to receive one of four doses of medication or placebo once daily for five days, before they enter the PCI.November 17, 2003The Alexion Pharmaceuticals Procter & Gamble mixed results from the Phase III trial investigating pexelizumab, C5 inhibitor anti-inflammatory and designed to treat patients undergoing surgery for coronary artery bypass graft bypass with the heart. The results showed that the primary endpoint did not meet statistical significance, but the drug did not achieve significant reductions in the end point of death / MI in the same secondary analysis of each additional. The primary endpoint was the incidence of death or myocardial infarction (death / MI) at postoperative day 30. Was reduced mortality / MI (9.8%) in the pexelizumab, compared to 11.8 with placebo. The study called PRIMO-CABG (Pexelizumab reduction in infarction and mortality in coronary heart bypass graft surgery), recording more than 3,000 subjects undergoing surgery CABG. The results were presented at the American Heart Association Scientific Sessions in Orlando, Florida.Esperion Therapeutics reported positive results from Phase II trial investigating ETC-216 (Almaty Programme of Action-I Milano / phospholipid complex) for the treatment of atherosclerosis. The results of this drug rapidly reduce the size of deposits in the coronary arteries and reverse the hardening of the arteries. The data revealed statistically significant reduction in the size of the Panel percent in the groups combined ETC-216 treatment compared to the end of treatment values to baseline values. The overall rates of adverse events similar in all three treatment groups and ETC-216 is generally well tolerated. The study enrolled 47 people with acute coronary symptoms. Five subjects received intravenous infusion weekly placebo or ETC-216 (15-45 mg / kg).Results were reported in the November 2003 issue of the Journal of the American Medical Association.October 6, 2003AVI BioPharma reported positive results from Phase II trial investigating Resten-NG, a drug Neugene drugs for the treatment of cardiovascular restenosis. The results showed restenosis rate from 33.3% in the control of both, and 3 mg dose treatment groups, at a rate of 8.3% in a dose of 10mg. And 10mg dose group showed a significant reduction of late loss, and a decrease in vessel lumen diameter at six months, and the length of the lesion, compared with the control of both groups and 3mg. Were not there is an increase in toxicity or adverse events in any of the treatment groups. Enrolled in the multicenter, randomized, controlled study, called the feasibility of 0.57 threads. Trial evaluating the safety and effectiveness of Resten-NG in the material at high risk of restenosis after angioplasty heart and blood vessels and the development of stents.Results were reported in 15 annual scientific symposium of the medication through the catheter cardiovascular in Washington, DCThe Scios positive results from a pilot study to investigate Natrecor (nesiritide), and recombinant human B-type Natriotrak peptide for the treatment of congestive heart failure. The results showed that was well tolerated in the Natrecor infusion weekly for 12 weeks.Were discontinued in less than 1% (11 of 1645) of the pump because of side effects. The data showed that the occurrence of adverse events was similar in the three groups, and there is no adverse event occurred a significant increase in often in groups of Natrecor. The multicenter, randomized, three-treatment arm, open-label, study enrolled 210 subjects at risk for rehospitalization. The design of this study was to evaluate the safety and tolerability of weekly injection of Natrecor administered in outpatient clinics to identify people who were at high risk of hospitalization. The results were presented at the Annual Scientific Meeting 7 of the heart failure society of America in Las Vegas. <September 8, 2003The heart of the final results of the positive experience of the medical staff to investigate and CYPHER sirolimus, eluting coronary stents to treat clogged arteries. The results showed steady improvement in vessel re-narrowing in the month of follow-up -12 versus regular traditional metal stents. The data also showed a trend toward lower rates of re-blockage of the subjects treated with the Cypher pillars without the prior expansion. The results showed earlier that 43.6% of people who received the standard metal stents offered reblockage compared with 5.8% of subjects treated with the CYPHER. He joined the study, called E-SIRIUS 352 Topics in 35 locations in Europe. The results were presented at the European Society Congress 2003 in the heart and blood vessels in Vienna.According to King Pharmaceuticals Wyeth positive results from post-marketing trial to investigate Altace (ramipril), the ACE inhibitor for the prevention of cardiovascular disease. The results showed the existence of sustainable impact of ramipril on the prevention of diseases of the heart and blood vessels was carried out any preventive effect of vitamin E. The study by the Population Health Research Institute at McMaster University and Hamilton Health Sciences in Hamilton, Ontario, Canada. The results were presented at a conference of the European Society of Cardiology meeting in Vienna, Austria. Started HOPE-very (HOPE-the results of ongoing) study in November 1999, and studied the benefits seen with 4.5 years of treatment with continued ramipril and whether long-term treatment with vitamin E to protect against the development of cancer and diseases of the heart and blood vessels .Novartis reported positive results from clinical trials investigated everolimus, a drug for the treatment of immune complications of heart transplantation. The results showed that everolimus significantly more effective in reducing the severity and the incidence of serious complications of transplantation of the current treatment. The data also showed that everolimus significantly reduced the prevalence of infection cytomegalovirus. The international study was conducted for two years in 52 medical centers in four countries, and enrolled 634 people with heart transplants that were given the standard regimen of cyclosporine and steroids, in addition to drug treatment. Has been designed this study to target acute rejection and heart disease morbidity and vascular allograft. The results were presented in Issue 28 August of the New England Journal of medicine.March 10, 2003The Texas Biotechnology and Glaxo Smith Kline positive results from Phase II trial investigating Argatroban, a synthetic thrombin inhibitor for the treatment of a direct stroke. The results showed drug-producing intracranial hemorrhage (ICH) rate compared with placebo. Was successfully received by the primary endpoint of safety, defined as intracranial bleeding symptoms within 30 days, confirmed by CT, with no statistically significant differences between the treatment group versus placebo. Final results showed that high school, defined as symptoms of ICH, major systemic hemorrhage, bleeding slightly irregular, and the effectiveness of each group, stroke, there are significant differences from placebo.Registered double-blind, randomized study, called ARGIS-I (Argatroban in acute ischemic stroke), and 176 stroke subjects.Topics presented and Argatroban or placebo for two different levels of anticoagulation within 12 hours of the onset of symptoms.January 27, 2003Spectranetics reported positive results from pivotal Phase II trial investigating Lacey (laser catheter parties critical ischemia), an experimental device for the treatment of limb ischemia. The data that have been achieved in the primary endpoint, a six-month survival with limb salvage, in 93% of the treatment compared to 87% in the control group. The results showed a significant adverse events in subjects treated was approximately 50% less than those of the control group. Trial enrolled 145 people who were poor surgical candidates in the United States 14, and several European sites. The data were compared to a control group trial consisting of 789 people with critical limb ischemia treated with a variety of standard treatments.October 7, 2002The provisional results of the Phase II trial ongoing Resten-NG was effective in preventing coronary artery restenosis after angioplasty and stent put for treating lesions of atherosclerosis. The selection of a set of three treatment groups, including the control group which received no drug treatment and two who received a dose of 3 or 10 mg of Resten-NG. After six months follow-up, and the people who received 10 mg of Resten-NG rate of restenosis 11% reduction of 80% in the restenosis while the control group, and mg 3 of Resten-NG group averaged approximately 50% return stenosis rate. AVI BioPharma develops Resten-NG.July 22, 2002Esperion Therapeutics reported positive results from the first phase of the trial of 642, and others in subjects with stable atherosclerosis.Included trial, which evaluated five dose levels of pumping one ETC-642 intravenous .28 people who were monitored for four weeks after dosing. The results showed that ETC-642 was safe and well tolerated at all dose levels tested. In addition, the data showed evidence of increases in HDL-cholesterol levels and the rapid mobilization of cholesterol.June 17, 2002Were reported positive results from the first phase of the trial of AC3056, a compound for the treatment of examination of atherosclerosis and other conditions related to blockage of blood vessels. In double-blind, crossover placebo-controlled trial, received 14 people healthy oral formulation of AC3056 in a dose-escalating.The results showed a dose-dependent increases in blood levels of AC3056, as well as dose-dependent increase in the activity of antioxidants in the blood. The drug was well tolerated with no safety concerns. AC3056 is being developed drug-amylin.
Missing Data Lead FDA Panel to Vote Against Rivaroxaban for ACS May 23, 2012 (Updated May 24, 2012) (Silver Spring, Maryland) — The missing data issues plaguing the ATLAS ACS 2 TIMI 51 trial of the factor Xa inhibitor rivaroxaban (Xarelto, Bayer Healthcare/Janssen Pharmaceuticals) have prevented the drug from earning the endorsement of the FDA Cardiovascular and Renal Drugs Advisory Committee. At its May 23 meeting, the panel voted six to four (with one abstention) against recommending that the FDA approve rivaroxaban for reducing the risk of thrombotic cardiovascular events in patients with acute coronary syndrome or unstable angina in combination with aspirin, aspirin plus clopidogrel, or ticlopidine. Janssen's application is based on the results of the ATLAS ACS 2 phase 3 and the ATLAS ACS TIMI 46 phase 2 trial. The placebo-controlled ATLAS ACS 2 showed rivaroxaban reduced the risk of both all-cause and cardiovascular mortality while increasing the risk of bleeding and intracranial hemorrhage, but the studies were hindered by early patient withdrawals and missing data. We Don't Know What We're Missing Based on the ATLAS ACS 2 results, FDA reviewer Dr Karen Hicks recommended approval of rivaroxaban for the requested indications except all-cause mortality. However, another FDA reviewer, Dr Thomas Marciniak, was adamant that the trial results are not interpretable because about 12% of the patients had incomplete follow-up, far higher than the 1% to 1.5% differences in the end-point rates between rivaroxaban and placebo. A total of 1294 subjects discontinued the trial prematurely, and the company was only able to contact 183, of which 177 were confirmed to be alive. Because of the patient dropouts, the company adopted a "modified intention-to-treat analysis," whereby patients were observed for 30 days after randomization or the global end date for the trial, instead of observing all the patients until the end of the trial as the FDA originally suggested. Marciniak criticized the sponsor's efforts to follow the patients and said that three patient deaths not counted in the modified intention-to-treat analysis may just be the "tip of the iceberg." Because the percentage of patients whose ultimate vital status remains unknown is much greater than the reported differences in mortality rates, the claimed mortality benefits are not reliable. The majority of the panel sided with Marciniak. For example, Dr Sanjay Kaul (University of California, Los Angeles) voted "no" because "there was enough uncertainty in the quality and robustness of the data that dissuaded me from voting yes. . . . The 'missingness' of the data doesn't invalidate it, but it certainly makes it hard to infer [the conclusion]." Dr Steven Nissen (Cleveland Clinic, OH) said that the decision to use the modified intention-to-treat analysis had a "profound impact" on the interpretability of the data. "It's saying we don't care what happens after 30 days, [and] that colored the trial in ways we couldn't recover from." Given the risk of major bleeding, "I want to see better evidence that this strategy of adding an Xa inhibitor or a direct thrombin inhibitor or something else to a good antiplatelet agent is robustly better for the patient," Nissen said. He recommends that the companies run a new trial of the 2.5 twice-daily dose of rivaroxaban using a strict intention-to-treat approach, but, he said, "I don't expect the death benefit to be too robust." Several panelists said they were concerned that the patients who dropped out of the trial were disproportionately likely to have a bleeding event, which led them to quit the trial, or a "protopathic" event, as statistician Dr Scott Emerson (University of Washington, Seattle) put it. "We're worried that an impending event is what is changing their behavior. We see that all the time in clinical trials--that regularly measured end points do not pick up [all of] the events," he said. He said that since the company was only able to contact 183 of the over 1200 patients who dropped out, it is possible that the dropouts skew the outcomes comparison of the trial. "Differential event rates after dropout are the number-one thing we're afraid of, so you have to explore it" in a statistical sensitivity analysis of the potential impact of these unknown outcomes. "It would not surprise me if, at the end of the day, these data did not hold up under a proper sensitivity analysis," he said. "What I want to know is, among the people who had events, how differential was the follow-up, but I can tell you by just looking at it, there was a very slightly different amount of follow-up of the people in the treatment arm. But I don't know whether everyone in the treatment arm was cured and they were trekking in the Himalayas and everyone in the placebo arm went home to die. I don't know that that's not the case." Dr Maury Krantz (University of Colorado, Denver) voted in favor of approval but said he does not know how rivaroxaban would perform in general clinical practice, especially when used with aspirin and clopidogrel. "I felt very much torn by this. This isn't a simple paradigm shift. It means going to triple therapy, which is really a three-headed monster in many ways. I think that what you're going to see in practice, if this is not done carefully with the proper labeling and secondary studies, is really dramatic magnification of bleeding and perhaps minimization of the efficacy benefit."
May 23, 2012 (Updated May 24, 2012) (Silver Spring, Maryland) — The missing data issues plaguing the ATLAS ACS 2 TIMI 51 trial of the factor Xa inhibitor rivaroxaban (Xarelto, Bayer Healthcare/Janssen Pharmaceuticals) have prevented the drug from earning the endorsement of the FDA Cardiovascular and Renal Drugs Advisory Committee. At its May 23 meeting , the panel voted six to four (with one abstention) against recommending that the FDA approve rivaroxaban for reducing the risk of thrombotic cardiovascular events in patients with acute coronary syndrome or unstable angina in combination with aspirin, aspirin plus clopidogrel , or ticlopidine . Janssen's application is based on the results of the ATLAS ACS 2 phase 3 and the ATLAS ACS TIMI 46 phase 2 trial. The placebo-controlled ATLAS ACS 2 showed rivaroxaban reduced the risk of both all-cause and cardiovascular mortality while increasing the ri...
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