The following data were presented at the American Heart Association Scientific Sessions 2016 in New Orleans.
Akcea Therapeutics Inc., of Cambridge, Mass., a wholly owned subsidiary of Ionis Pharmaceuticals Inc., presented results from an interim analysis of a phase I/IIa study of IONIS-ANGPTL3-LRx, showing that subjects with elevated triglycerides achieved substantial and statistically significant mean reductions in angiopoietin-like 3, or ANGPTL3, triglycerides and LDL-cholesterol of up to 83 percent, 66 percent and 35 percent, respectively. Subjects who received multiple doses of 10 mg, 20 mg, 40 mg or 60 mg of IONIS-ANGPTL3-LRx achieved dose-dependent, statistically significant mean reductions at day 37 in ANGPTL3 of up to 83 percent (p ≤0.001). They also experienced statistically significant mean reductions in triglycerides of up to 66 percent (p ≤0.001), in LDL-C of up to 35 percent (p ≤0.001) and in total cholesterol of up to 36 percent (p ≤0.001).
Amarin Corp. plc, of Dublin, reported data that further characterized the efficacy and safety of Vascepa (icosapent ethyl) in statin-treated women with persistent high triglyceride levels. The presentation of additional data from the ANCHOR study showed, consistent with overall study results, that prescription-pure EPA Vascepa reduced triglyceride levels and several other potentially atherogenic lipid parameters and inflammatory markers in a subgroup of statin-treated women with persistent high triglycerides. The post hoc analysis is published in the American Journal of Cardiology. Vascepa capsules are a single-molecule prescription product consisting of either 1 gram or 0.5 grams of the omega-3 acid commonly known as EPA in ethyl-ester form.
Amgen Inc., of Thousand Oaks, Calif., said that adding Repatha (evolocumab) to optimized statin therapy resulted in statistically significant regression of atherosclerosis in patients with coronary artery disease, according to data from the phase III GLAGOV coronary intravascular ultrasound imaging trial. GLAGOV evaluated whether the PCSK9 inhibitor would modify atherosclerotic plaque buildup in the coronary arteries of patients already treated with optimized statin therapy, as measured by intravascular ultrasound at baseline and week 78. Treatment with Repatha resulted in a statistically significant regression from baseline in percent atheroma volume (PAV), with those in the Repatha arm experiencing a 0.95 percent decrease vs. baseline in PAV compared with an increase of 0.05 percent vs. baseline in patients receiving optimized statin therapy plus placebo (p<0.0001). In addition, adding Repatha yielded plaque regression in PAV for a greater percentage of patients than for those receiving placebo (64.3 percent vs. 47.3 percent, respectively, p<0.0001).
Arrowhead Pharmaceuticals Inc., of Pasadena, Calif., reported preclinical data for its lipoprotein(a)-targeting candidate, ARC-LPA, and its factor XII-targeting candidate, ARC-F12, both of which the company said showed substantial improvements over previous RNAi-based generation triggers. Among the data presented included dose-dependent reductions in serum F12 levels observed with single injections of anticoagulant ARC-F12 of 1 mg/kg and 3 mg/kg, leading to mean reductions of 86 percent and 96 percent, respectively. In a rat arteriovenous shunt model, a statistically significant reduction (p=0.002) in thrombus weight was observed at greater than 95 percent F12 knockdown. Nonhuman primate studies of ARC-LPA showed a reduction of 85 percent to 90 percent of serum Lp(a) levels after three weekly 3-mg/kg SQ doses. In an atherosclerosis model, data suggest that RNAi triggers can be effectively delivered to a fatty liver using Arrowhead’s DPCsq platform.
Boehringer Ingelheim GmbH, of Ingelheim, Germany, presented updated results from 494 patients in its ongoing phase III RE-VERSE AD study, showing that administration of 5 g of idarucizumab immediately reversed the anticoagulant effect of dabigatran, the active ingredient in Pradaxa (dabigatran etexilate mesylate). For group A patients with extracranial bleeding, median time to confirmation of hemostasis was 3.5 to 4.5 hours, depending on anatomical location. The source of bleeding was similar to the previous interim analysis. In group B, 93 percent of patients experienced normal hemostasis during surgery, and the median time to the operating room was 1.6 hours after administration of idarucizumab. Idarucizumab, marketed in the U.S. as Praxbind, gained approval as a specific reversal agent for the firm’s oral anticoagulant. (See BioWorld Today, Oct. 9, 2015.)
CSL Behring, of King of Prussia, Pa., reported results from AEGIS-I, a phase IIb trial testing CSL112, an apolipoprotein A-I infusion therapy in development to reduce the high incidence of early recurrent cardiovascular events that occur in the weeks to months following a heart attack, most commonly due to additional rupture of vulnerable atherosclerotic plaque. AEGIS-I met its co-primary safety endpoints, showing that CSL112 does not cause significant changes in liver or kidney function and demonstrating that it is well-tolerated when administered in the acute myocardial infarction setting. The study also provided confirmation of CSL112’s mechanism of action, cholesterol efflux enhancement, as demonstrated by an immediate, up to fourfold increase in cholesterol efflux capacity, compared to baseline. Results were published online in Circulation.
Cytokinetics Inc., of South San Francisco, reported additional results from its COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure) phase II trial evaluating omecamtiv mecarbil in patients with chronic heart failure and left ventricular systolic dysfunction. Results showed that omecamtiv mecarbil, an investigational cardiac myosin activator, improved left atrial (LA) structure and function in patients with chronic heart failure with reduced systolic function. Analysis showed that minimum and maximum left atrial volume (LAV) decreased over time, with a statistically significant reduction in minimum LAV at 20 weeks (p=0.032) in patients receiving omecamtiv mecarbil. Similarly, patients receiving omecamtiv mecarbil experienced statistically significant improvements in LA emptying fraction at 12 and 20 weeks (p=0.018 and p=0.004, respectively). The drug is being developed with Thousand Oaks, Calif.-based Amgen Inc.
Novartis AG, of Basel, Switzerland, presented results of a new analysis demonstrating that Entresto (sacubitril/valsartan) tablets reduced the risk of all events – first and repeat heart failure (HF) hospitalizations as well as cardiovascular (CV) deaths that followed HF hospitalization – compared to enalapril among heart failure patients with reduced ejection fraction (HFrEF). The findings are from a post-hoc analysis of PARADIGM-HF, in which a total of 3,181 primary endpoint events (including 1,251 CV deaths) were observed during the median 27-month double-blind follow-up period. Using multiple statistical analysis models, investigators found that Entresto demonstrated a risk reduction of between 20 percent to 24 percent for all events (first-time and repeat events) compared to enalapril, findings that were consistent with the proven benefit of Entresto for reducing the risk of a first event in PARADIGM-HF (a 20 percent risk reduction compared to enalapril on the primary endpoint, a composite measure of time to CV death or first HF hospitalization).
Portola Pharmaceuticals Inc., of South San Francisco, reported results from three substudies of the pivotal phase III APEX Study of betrixaban, an oral, once-daily factor Xa inhibitor anticoagulant in development for the prevention of venous thromboembolism in acute medically ill patients. In a retrospective APEX substudy on stroke, researchers assessed the potential of extended-duration thromboprophylaxis with betrixaban compared with standard-dose enoxaparin to reduce the risk of stroke in hospitalized acute medically ill patients. Results found that extended-duration betrixaban significantly reduced all-cause stroke (0.54 percent for betrixaban vs. 0.97 percent for enoxaparin; RRR=44 percent) and ischemic stroke (0.48 percent for betrixaban vs. 0.91 percent for enoxaparin; RRR=47 percent) through 77 days of follow up. Findings were published in Circulation.
Viking Therapeutics Inc., of San Diego, reported data from its phase Ib trial of VK2809 in subjects with mild hypercholesterolemia, with an analysis of the study participants’ atherogenic protein levels demonstrating that subjects experienced statistically significant reductions in lipoprotein(a), or Lp(a), and apolipoprotein B-100 (apo B). Following 14 days of VK2809 treatment, subjects experienced statistically significant placebo-adjusted, least square mean reductions in both Lp(a) and apo B across a range of doses. Reductions in apo B ranged from 20.2 percent at 5 mg (p = 0.0008) to 39.6 percent at 40 mg (p < 0.0001); reductions in Lp(a) ranged from 31.6 percent at 5 mg (p = 0.12) to 54.9 percent at 20 mg (p = 0.002). Comparable results were obtained with or without least square mean adjustments, which account for covariates in patient characteristics. VK2809 is an orally available small-molecule thyroid receptor agonist.