Despite the shortage of space on the trams to and from the Amsterdam RAI Center, and despite the shortage of official conference bags and programs, there was no shortage of interesting new research and debate at the ESC Congress 2013 in Amsterdam. Here, I provide a brief overview of some of the research highlights from this year's ESC conference in Amsterdam.
The Hot Line Sessions started off on a positive note with the Hokusai-VTE study demonstrating that Daiichi-Sankyo's Factor Xa (FXa) inhibitor edoxaban (Lixiana) was non-inferior for the primary efficacy outcome of recurrent VTE, and superior for the primary safety outcome of major or clinically relevant non-major bleeding , when compared with low-molecular weight heparin (LMWH) plus warfarin. Good news for Daiichi Sankyo; but, we feel that uptake of this agent will be restricted due to the requirement for a LMWH lead-in. Further analysis of this study is available here.
In the Phase III ACCOAST trial, designed to test the benefits of prasugrel (Eli Lilly/Daiichi Sankyo's Effient/Efient) preloading in NSTEMI patients, there was no difference in the primary efficacy end point, but prasugrel preloading increased both surgical and non-surgical TIMI major bleeding episodes through day 7. Indeed, the trial was halted early in November 2012 due to excessive bleeding and lack of ischemic benefit. This result follows the failure of the TRILOGY-ACS study in which prasugrel demonstrated non-inferiority to clopidogrel in medically managed UA and NSTEMI patients. While the fears regarding increased bleeding with prasugrel will not be allayed by the failure of the ACCOAST trial, the results are not expected to alter cardiologists? current treatment strategies with the drug.
Another negative ACS trial was the TAO study, investigating Sanofi's intravenous direct factor Xa inhibitor otamixaban compared with unfractionated heparin plus eptifibatide (Merck/GlaxoSmithKline's Integrilin) in PCI-treated NSTEMI patients. Sanofi decided to discontinue the development of otamixaban in June, when negative top-line results were first reported. This result should shore up unfractionated heparin's role in ACS, provide further growth opportunity to bivalirudin (The Medicines Company's Angiomax/Angiox), and also provide a boost for the prospects of Regado Bioscience's REG-1 anticoagulation system.
ATOMIC-AHF: Omecamtiv mecarbil
While the Phase II ATMOIC-AHF did not meet its primary end point (reducing dyspnea), there is still some optimism omecamtiv mecarbil (Amgen/Cytokinetics), a drug that increases stroke volume apparently without upping myocardial oxygen demand or promoting arrhythmias. While development of both formulations has progressed separately, the ultimate development goal is to move toward initiation of a Phase III trial with both the IV and oral formulations. This is an agent that has struck a chord with interviewed thought leaders who express enthusiasm for an inotropic agent that does not have the side effects of currently available therapies. They also find the idea of a drug therapy that is available in both oral and IV formulations appealing because it could enable a seamless transition from the acute to the chronic setting. Amgen are currently awaiting data from another Phase II trial, Cosmic-HF, which is investigating an oral version of the drug in patients with chronic heart failure, before deciding whether to continue with the drug.
Finally, to keep up the theme, another negative trial from Resverlogix's RVX-208, but with a twist. While overall results from the Phase II ASSURE-1 intravascular ultrasound (IVUS) study demonstrated that RVX-208 failed to show significant regression of atherosclerosis versus placebo. Once again, RVX-208 failed by a narrow margin to meet significance in the primary end point?change from baseline in percent atheroma volume (p=0.08). Similarly, in the Phase II ASSERT trial, presented at the 2010 AHA meeting, the top dose of RVX-208 (150 mg BID) also narrowly failed to meet statistical significance in the primary end point?change in plasma apo A-I levels (p=0.06). However, further analysis of the ASSURE-1 data has revealed that patients taking rosuvastatin (AstraZeneca/Shionogi's Crestor) and RVX-208 had a statistically significant plaque regression of -1.43% (p<0.002), which well surpassed the prespecified primary end point of -0.6%. This result would suggest that rosuvastatin and RVX-208 exert a synergistic effect on atherosclerotic lesion regression when combined.
Conor Walsh is a Senior Director on the Cardiovascular, Metabolic and Renal Disorders team at Decision Resources Group.