Unmet Needs
Unmet Needs 2016: Atherosclerosis
November 6, 2016

Cardiovascular disease is the leading cause of death worldwide. In the U.S., there are approximately 11 million people with atherosclerotic cardiovascular disease (ASCVD) and/or familial hypercholesterolemia (FH) who have uncontrolled levels of low-density lipoprotein (LDL-C) over 70 mg/dL, despite treatment with statins or other cholesterol-lowering therapies. More than 60 percent of high-risk patients in Europe are still unable to adequately lower their LDL-C levels with statins or other currently approved lipid-lowering agents. Among very high-risk patients, the percentage is increased to more than 80 percent. It is estimated that less than one percent of people with FH (heterozygous and homozygous forms) in most countries are diagnosed.

Unmet needs in the management of atherosclerotic cardiovascular disease: Is there a role for emerging anti-inflammatory interventions? Lorenzatti AJ, Retzlaff BM. Int J Cardiol. 2016 Oct 15;221:581-6. doi: 10.1016/j.ijcard.2016.07.061. Epub 2016 Jul 5.


Atherosclerotic cardiovascular disease is the leading cause of death worldwide. Despite extraordinary advances in the understanding of the pathophysiology and the utilization of very effective medications such as statins, there still remains a significant residual risk. In fact, even after optimal interventional and medical therapy, the possibility of recurrent myocardial infarction remains at approximately one third for five years after acute coronary syndromes, thus emphasizing the urgent need for novel therapies to prevent the progress of atherosclerosis. In addition, over the past two decades, although atherosclerosis has been clearly identified as an inflammatory disease of the arterial wall from compelling data of animal and human studies, clinical applications related to this accumulated knowledge are scarce.

In addition to the current LDL-lowering therapies, extensive research is still required on the role of anti-inflammatory and/or immune-modulating drugs in targeting the inflammatory component of atherogenesis. To date, the strategy of using inflammatory modulation for the prevention and treatment of ASCVD remains unproven.

There is growing evidence of different pro-inflammatory pathways being involved in the atherosclerotic process. Thus, taking into account the role of IL-1β in atherosclerosis, the principle of applying anti-IL-1 therapy to reduce CV risk is a matter of crucial interest, which promises to provide important future benefits in the treatment of ASCVD.

Two large-scale clinical trials based on this approach are presently underway. In CIRT, low-dose MTX is being used as a broad-spectrum upstream anti-inflammatory therapy; and in the CANTOS study, the selective IL-1β monoclonal antibody canakinumab is targeted toward vascular inflammation. Both studies are expected to provide critical findings to help reduce the rates of recurrent MI, stroke, and CV death among stable CAD patients who remain at risk due to a persistent proinflammatory response.

As neither of these anti-inflammatory interventions seems to have a great impact on plasma lipid levels, this makes these approaches more promising for testing the pure inflammatory hypothesis than other significantly different emerging treatments, such as anti-TNF-α or anti-IL- 6, which have shown adverse lipid modifications. Indeed, CIRT and CANTOS should help to provide the clinical community with additional evidence to determine whether reducing inflammation can reduce CV event rates.

Amgen Announces Positive Top-Line Results From Phase 3 GLAGOV Imaging Study Of Repatha® (Evolocumab)


First Study to Demonstrate That Lowering LDL Cholesterol With a PCSK9 Inhibitor Impacts Underlying Atherosclerotic Disease on top of Optimized Statin Therapy

Amgen (NASDAQ:AMGN) today announced that the Phase 3 GLAGOV (GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound) trial evaluating the effect of Repatha® (evolocumab) on coronary artery disease (CAD) met its primary and secondary endpoints. The GLAGOV study is a large serial coronary intravascular imaging trial designed to test whether treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor Repatha modifies atherosclerotic plaque build-up in the coronary arteries of patients already treated with optimized statin therapy.

Detailed results from the Phase 3 GLAGOV trial will be presented during the upcoming American Heart Association (AHA) Scientific Sessions 2016 on Tuesday, Nov. 15, 2016, between 10:45 a.m. – noon CST.

“We are pleased with the positive results of this landmark study showing that Repatha modifies the underlying process of atherosclerosis,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “We strongly believe in the potential of Repatha to aid in the fight against cardiovascular disease, and we are excited to share these data with the scientific community at the AHA Scientific Sessions.”

GLAGOV is a Phase 3, multicenter, double-blind, randomized, placebo-controlled trial evaluating the impact of Repatha, a PCSK9 inhibitor, on coronary atheroma volume in 968 patients with CAD receiving optimized statin therapy and undergoing coronary catheterization. Patients were randomized to receive either monthly Repatha 420 mg or placebo subcutaneous injections.

No new safety concerns were identified in the GLAGOV trial. The incidence of treatment-emergent adverse events was comparable among both groups.

Harper continued, “Atherosclerosis is the major underlying cause of cardiovascular disease, which remains the leading cause of death worldwide. Now one year after the FDA approved Repatha, nearly two-thirds of patients prescribed Repatha are still being denied access. We are concerned that many patients with uncontrolled LDL cholesterol levels continue to face challenges in accessing a medicine that we now know has a positive impact on plaque burden.”

Admera Health Launches Molecular Test for Inherited Early Atherosclerosis Diagnosis and Risk


SOUTH PLAINFIELD, N.J., March 17, 2016 (GLOBE NEWSWIRE) — Admera Health (http://www.admerahealth.com), a commercial stage New Jersey based Precision Medicine and Digital Health company announced today the launch of AtheroGxOne™ following its approval by the New Jersey Department of Health. AtheroGxOne™ is a comprehensive Next Generation Sequencing (NGS)-based 84-gene panel aimed at identifying patients with a genetic signature for inherited premature coronary or atherosclerotic disease, such as Familial Hypercholesterolemia, as well as Mature Onset Diabetes of the Young (MODY).

Alterations in the panel genes can affect the metabolism of lipids and carbohydrates and lead to early atherosclerosis if left untreated. These diseases have a significant impact on cardiovascular risk since they appear at an early age and indicate a poor prognosis without aggressive medical intervention. In fact, approximately 5% and 20% of myocardial infarctions in individuals under 60 and 45 years of age, respectively, are due to alterations in the genes included in the panel.

Complementary Diagnostic Test for Familial Hypercholesterolemia

The AtheroGxOne™ panel can detect familial hypercholesterolemia (FH), a genetic disorder affecting 1 in 500 people that is characterized by high cholesterol levels, specifically very high LDL (“bad cholesterol”). People with FH are less likely to respond to usual interventions such as dietary modification or statin use, but they may be eligible for a new generation of PCSK9 inhibitor drugs, such as Repatha™ and Praluent™.

Developed as a joint venture between Admera Health and Health In Code (HIC), the test detects genomic variations associated with familial hypercholesterolemia, mixed hyperlipidemia, hypolipidemia and MODY. A comprehensive interpretive report is generated based on the integration of AtheroGxOne™ results with genetic and clinical information from HIC’s proprietary knowledge base containing more than 85,000 individuals. Reviewed by expert cardiologists specialized in genetics, AtheroGxOne™results provide cardiologists with clear genetic interpretation for risk assessment and disease diagnosis.

Dr. Guanghui Hu, President and CEO of Admera Health noted, “The approval of our AtheroGxOne™ test demonstrates once again the company’s ability to coordinate our R&D efforts with the work of our external partners to rapidly develop a best-in-class product that meets important unmet clinical needs. This new product, together with our other cardiovascular portfolio products, will help our company successfully meet or exceed our financial goals for the new year.”

Zeil Rosenberg, M.D., Admera Health’s VP for Medical Affairs, stated, “AtheroGxOne™ allows cardiologists to pinpoint genetic factors to help diagnose cholesterol and other lipid disorders, including Familial Hypercholesterolemia, at a much earlier phase of disease, opening up the potential for earlier medical intervention that can save lives. In addition, for endocrinologists, the panel provides genetic information for risk of Mature Onset Diabetes of the Young (MODY) where children otherwise diagnosed with insulin dependent diabetes can be taken off insulin and managed medically, avoiding a lifetime of injection therapy and increased risk for cardiovascular disease. Launch of the test marks a milestone in Admera Health’s portfolio expansion to meet the expressed needs of cardiologists to diagnose and to manage patients at-risk for inherited cardiovascular disease.”

The Admera Health Cardiovascular Test Portfolio

AtheroGxOne™ completes Admera Health’s unique Cardiovascular Test Portfolio, which includes CardioGxOne™ for inherited cardiac diseases and PGxCardio™ for pharmacogenomics testing. This comprehensive portfolio provides cardiologists with valuable information for risk assessment, diagnosis and treatment of a wide range of inherited cardiovascular diseases and conditions, including cardiomyopathies and sudden death, arrhythmias, lipid dysfunction and hypertension. Early risk assessment and diagnosis, as well as improved treatment decisions for cardiovascular diseases have a great potential to save lives and healthcare costs.