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PerkinElmer Expands Prenatal Screening Test Offerings, Introducing First Early Onset Preeclampsia Screening Test in the U.S.

PerkinElmer, a global leader in human and environmental health and an innovator in the field of prenatal screening for more than thirty years, announced today the first available early onset preeclampsia screening test in the United States. The PreeclampsiaScreen™ | T1 serum screening test enables physicians to more precisely detect asymptomatic patients in the first trimester of pregnancy who are at high risk for developing the dangerous condition, allowing for earlier identification, management and intervention. Early onset preeclampsia is a potentially serious condition that affects 0.5% of all pregnancies, often contributing more to the pregnant mother’s and baby’s risks of morbidity and mortality than does the late form of the disorder.

“This first of its kind screen is our latest commitment to providing clinicians with new, innovative ways to address some of today’s most challenging prenatal clinical scenarios,” said Jim Corbett, Senior Vice President and President, Diagnostics and Life Sciences & Technology for PerkinElmer. “Together with our recent advances, including offering a non-invasive prenatal test based on cell-free fetal DNA, plus a wide range of prenatal testing from biochemical screening to SNP microarray testing to detect birth defects and chromosome abnormalities, we’re giving physicians effective new tools for patient management.”

According to Dr. Jiri Sonek, MD RDMS, President, Fetal Medicine Foundation USA, and Adjunct Professor, Department of Obstetrics and Gynecology from Wright State University, “Preeclampsia is one of the remaining great challenges in obstetrics. It is a major cause of maternal, fetal, and neonatal morbidity and mortality. Fortunately, some physicians may recommend a simple and inexpensive intervention to reduce the risk of preeclampsia which is available in the form of low-dose aspirin. However, this treatment is effective only if begun early in pregnancy. That is why first trimester screening is such a critical component of preeclampsia prevention.”

Early onset preeclampsia is defined as preeclampsia, a sudden increase in blood pressure and protein in the urine, which leads to delivery of the fetus prior to 34 weeks’ gestation. If found early, options such as increased monitoring, modified activity, bed rest and medication can help reduce or avoid complications related to early onset preeclampsia.

PreeclampsiaScreen™ | T1 is administered during the first trimester of pregnancy through a simple blood test to detect three biochemical markers in the mother’s blood: PAPP-A (pregnancy-associated plasma protein-A); PlGF (placental growth factor) and AFP (alpha fetoprotein) that, when evaluated collectively with personal demographic data, provide an individual risk of developing early onset preeclampsia. Physicians have the option to provide two additional biophysical measurements for their patients — mean arterial pressure (MAP) and uterine artery Doppler pulsatility index (UtAD-PI) – each increasing the sensitivity of the screen when included in the testing protocol.

Source: PerkinElmer

The Search for an Early Biomarker to Fight Atherosclerosis

Recently, the Journal of the American Heart Association published conclusive results from a study directed by Dr. Éric Thorin of the Montreal Heart Institute (MHI), which suggests for the first time that a blood protein contributes to the early development of atherosclerosis.

Dr. Thorin, his team and his collaborators discovered that the blood levels of angiopoietin-like protein 2 (angptl2) are six times higher in subjects with coronary heart disease than in healthy subjects of the same age. Their basic research study also revealed that angptl2, which is undetectable in young mice, increases with age in healthy subjects and increases prematurely in subjects who have high cholesterol and pre-atherosclerotic lesions. Entitled “Angiopoietin-like 2 promotes atherogenesis in mice,” this study was conducted using an animal model consisting of three to twelve-month-old mice.

These results represent a major advance in the prevention and treatment of atherosclerosis. “Although much work remains to be done to broaden our knowledge of this protein’s mechanisms of action, angiopoietin-like protein 2 may represent an early biomarker not only to prevent vascular damage but also to predict atherosclerotic disease,” explained Dr. Thorin.

For 15 years, Dr. Thorin, a researcher at the MHI Research Centre and full professor at Université de Montréal, has been interested in the evolution of artery function during the aging process and in the underlying mechanisms of atherosclerosis. More specifically over the past five years, he has looked at the role of this particular protein. Thanks to his work, we now know that angptl2 causes a high degree of vascular inflammation. Blood levels of this protein increase in patients with cardiovascular disease as well as in people with complications related to diabetes, obesity and cancer in which the small blood vessels are damaged, as all of these diseases are associated with chronic inflammation.

According to Dr. Anil Nigam, a cardiologist and specialist in cardiovascular disease prevention at the MHI and co-author of the study, “Prevention is the ideal solution to delay the onset of atherosclerosis, and an early blood marker such as angptl2—if future clinical studies confirm this finding—will serve as an important tool to identify at-risk subjects who do not present with any symptoms of atherosclerotic disease.”

Study: Angiopoietin‐Like 2 Promotes Atherogenesis in Mice

Source: Montreal Heart Institute

CardioDx Announces Medicare Coverage for Corus CAD Gene Expression Test for the Diagnosis of Obstructive Coronary Artery Disease

CardioDx, Inc., a pioneer in the field of cardiovascular genomic diagnostics, recently announced data demonstrating that Corus® CAD, the only clinically validated gene expression test for the assessment of obstructive coronary artery disease (CAD), has higher diagnostic accuracy than commonly used risk assessment modalities including symptom evaluation and myocardial perfusion imaging (MPI) in women. The sex-specific analysis of the PREDICT (Personalized Risk Evaluation and Diagnosis in the Coronary Tree) Trial was presented during a poster session at the Women’s Health 2013: 21st Annual Congress, which took place in Washington D.C. from March 22 nd – 24th.

There is a growing body of clinical evidence confirming that standard diagnostic approaches used to evaluate patients for obstructive CAD lead to many unnecessary noninvasive and invasive procedures such as MPI, stress echocardiogram, computed tomography angiography and coronary angiography, especially in women[1]. According to the results of the PREDICT Trial, MPI was not a significant predictor of obstructive CAD in women. This may be due to the presence of breast and fatty tissue in women, which leads to a higher rate of false-positive diagnoses[2] and, consequently, a higher rate of unnecessary referrals for additional invasive testing. The study also found that chest pain and other clinical factors are not reliable predictors of obstructive CAD in women. The traditional chest pain symptom classification as defined by Diamond and Forrester is helpful in diagnosing men, but does not correspond to presence of obstructive CAD in women. Furthermore, women with obstructive CAD tend to present with atypical, nonspecific symptoms such as shortness of breath, fatigue, and abdominal pain. Only the Corus CAD score and dyslipidemia were associated with the findings of obstructive CAD in women.

“Since the symptoms of coronary disease in women are not as well defined as in men, clinicians cannot use the same assessment criteria in women as they do in men,” said Alexandra Lansky, MD, Associate Professor of Medicine and Director of the Cardiovascular Research Center, Yale University School of Medicine, the senior author of the study and one of the PREDICT co-investigators. “Women have more angina and less obstructive coronary artery disease compared to age-matched men and are significantly over-referred to invasive coronary angiography, as current noninvasive diagnostic approaches have limitations in women. Women need tests that are both specific to their biology and can reliably assess the origin of their symptoms. Corus CAD is the only sex-specific test for evaluating obstructive CAD and represents a paradigm shift in how clinicians may diagnose heart disease in women, who account for half of the U.S. population.”

The PREDICT cohorts analyzed included 1,160 stable non-diabetic men and women referred for cardiac catheterization with typical and atypical symptoms suggestive of obstructive CAD or who were asymptomatic with a high risk of CAD: a substudy of 492 women was included in this sex-specific analysis. Of the women referred to invasive coronary angiography with abnormal MPI results (N=295), only 22 percent had obstructive CAD upon invasive coronary angiography. The study showed that Corus CAD results were more accurate than MPI and were significantly associated with the extent and severity of obstructive CAD. Corus CAD was a significant classifier of obstructive CAD in the overall population (p<0.001) and in the male (p=0.001) and female (p<0.001) subgroups separately, whereas MPI was not found to be an independent indicator of obstructive CAD. Each 10-point increase in the Corus CAD score was associated with a twofold increase in the likelihood of obstructive CAD in men, and a 3.4-fold increase in the likelihood of obstructive CAD in women. The results demonstrate the improved ability of Corus CAD to safely exclude obstructive CAD as a diagnosis, particularly in women.

Separately, a poster confirming the clinical utility of Corus CAD in the primary care setting to accurately exclude the diagnosis of obstructive CAD in stable, symptomatic female patients was also presented at the Women’s Health Congress. The poster titled, “The Use of a Personalized Gene Expression Test to Improve Decision Making in the Evaluation of Women with Symptoms of Suspected Obstructive Coronary Artery Disease” represents a substudy that included 141 women of a 317 total patient population in this sex-specific analysis led by Michael Conlin, MD, Johns Creek Primary Care. Results showed that Corus CAD scores could reliably separate female patients into elevated risk (score ≥15) and low risk (score ≤15) groups, allowing primary care physicians to more accurately triage patients. Use of Corus CAD led to a reduction in referrals to cardiologists of 77 percent in the low-scoring female patient group (p<0.001).

“With test overutilization contributing to the approximately $5 billion in annual cardiac-related diagnostic costs in this population, primary care providers are concerned with accountable care now more than ever,” said Dr. Conlin. “As the symptoms in women are harder to diagnose, they are often referred to additional and more invasive testing that ultimately produces low yields of obstructive CAD. Therefore, we welcome sex-specific tools like Corus CAD to help us more effectively identify the right patients who need further noninvasive and invasive cardiac workup.”

Among the 141 women studied, 73 percent had low Corus CAD scores. PCPs referred 12 percent of patients with low scores and 48 percent with non-low scores to cardiology. Of the patients with low scores who underwent additional testing, none were found to have clinically significant obstructive CAD. The average follow-up duration was 163 days, and no patients experienced a major adverse event during this time. 

Source: CardioDx

The Medicines Company and Alnylam Form Strategic Alliance to Develop and Commercialize RNAi Therapeutics Targeting PCSK9 for the Treatment of Hypercholesterolemia

The Medicines Company (Nasdaq: MDCO) and Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, recently announced that they have formed an exclusive global alliance for the development and commercialization of Alnylam’s ALN-PCS RNAi therapeutic program for the treatment of hypercholesterolemia.

“This new alliance unites two organizations with a shared culture and commitment to innovation. In my view and past experience, there could be no stronger partner for our ALN-PCS program than The Medicines Company, which has demonstrated industry-wide leadership in the advancement of cardiovascular medicines to patients and remarkable success in its strategy of in-licensing, developing, and commercializing breakthrough products,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “For Alnylam, this new partnership enables the advancement of ALN-PCS, an important program within our ‘Alnylam 5×15’ product development and commercialization strategy focused on RNAi therapeutics directed toward genetically validated targets. We believe that the ALN-PCS program holds great promise for the development of a significant therapeutic option for patients with hypercholesterolemia, and that the unique mechanism of action for ALN-PCS could provide a differentiated and potentially best-in-class strategy for PCSK9 antagonism.”

“Our focus on acute and intensive care medicine has led us to a leadership position with Angiomax® (bivalirudin) and potentially with cangrelor in the management of patients in extreme risk as a consequence of the rupture of their vulnerable coronary artery plaque at and around the time of acute coronary syndromes. Meantime, we have made progress with MDCO-216 (ApoA-1 Milano), a turbocharged form of HDL-C (‘good cholesterol’) which has the potential to modify disease through reverse cholesterol transport,” said Clive Meanwell, M.D., Ph.D., Chairman and Chief Executive Officer of The Medicines Company. “Now, this exciting collaboration with Alnylam – leaders in their field of RNAi – adds a second potentially disease modifying approach and more cutting edge technology to our portfolio. We have seen that PCSK9 gene silencing can substantially reduce LDL-cholesterol in patients and has epidemiological and disease mechanisms studies suggest this can further reduce the risks of the world’s number one killer, coronary artery disease. Clearly we see the complementarity of approaches which increase ‘good cholesterol’ (HDL-C) and decrease ‘bad cholesterol’ (LDL-C). We look forward to working with our colleagues at Alnylam for whom we have the greatest respect and admiration based upon earlier collaborations particularly around Angiomax, which was invented by John Maraganore.”

PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein that regulates low-density lipoprotein (LDL) receptor levels on hepatocytes; gain-of-function human mutations in PCSK9 are associated with hypercholesterolemia while loss-of-function mutations are associated with lower levels of LDL cholesterol and a reduced risk of cardiovascular disease. ALN-PCS is a PCSK9 synthesis inhibitor that reduces intracellular and extracellular levels of PCSK9 resulting in lowered plasma levels of LDL-C. MDCO-216 is a naturally occurring variant of a protein found in high-density lipoprotein, or HDL. It is a reverse cholesterol transport agent designed to reduce atherosclerotic plaque burden development and thereby reduce the risk of adverse thrombotic events.

Under this alliance, The Medicines Company and Alnylam intend to collaborate on the advancement of the ALN-PCS program. Alnylam’s ALN-PCS program includes ALN-PCS02 – an intravenously administered RNAi therapeutic which has completed a Phase I trial, and ALN-PCSsc – a subcutaneously administered RNAi therapeutic currently in pre-clinical development. Alnylam will continue the program for an estimated one to two years to complete certain pre-clinical and Phase I clinical studies. The Medicines Company is responsible for leading and funding development from Phase II forward and commercializing the ALN-PCS program if successful. Under the terms of the agreement, The Medicines Company will make an upfront cash payment of $25 million to Alnylam. Alnylam may also receive potential development and commercial milestone payments of up to $180 million. Alnylam will be eligible to receive scaled double-digit royalties on global products sales of ALN-PCS products.

Alnylam has completed a Phase I trial of ALN-PCS02 in healthy volunteer subjects with elevated baseline LDL-C. Results showed that administration of a single intravenous dose of drug, in the absence of concomitant lipid-lowering agents such as statins, resulted in statistically significant and durable reductions of PCSK9 plasma levels of up to 84% and lowering of LDL-C of up to 50%. ALN-PCS02 was shown to be generally safe and well tolerated in this study and there were no serious adverse events related to study drug administration. Alnylam has also presented pre-clinical data from its ALN-PCSsc program demonstrating potent knockdown of the PCSK9 target gene with an ED50 of less than 0.3 mg/kg after a single subcutaneous dose.

“Cardiovascular disease remains the leading cause of mortality worldwide, with elevated LDL-C a major modifiable risk factor. New strategies are needed to dramatically and rapidly reduce LDL-C and prevent acute cardiovascular events that result from the rupture of cholesterol rich plaque when patients are at their most vulnerable,” said Daniel J. Rader, M.D., professor of Medicine and chief, Division of Translational Medicine and Human Genetics, at the Perelman School of Medicine at the University of Pennsylvania. “As a key regulator of the LDL receptor, liver-expressed PCSK9 is one of the most important and best validated new targets in molecular medicine for the treatment of hypercholesterolemia. The ALN-PCS data generated to date are very encouraging and I look forward to continued clinical studies that highlight the unique mechanistic approach of PCSK9 synthesis inhibitors.”

Dr. Rader serves as a member of Alnylam’s Scientific Advisory Board and as a consultant on Alnylam’s ALN-PCS program, and Alnylam and Dr. Rader collaborate on research for which Alnylam provides materials.

Source: The Medicines Company

Shiel Medical Laboratory’s Oxidized LDL Triple Marker Test Uncovers Symptoms of Latent Heart Disease Better than Standard Lipid Test

The primary clinical laboratory test used by physicians to identify patients with coronary artery disease (CAD) fails to measure oxidized low-density lipoprotein (LDL), the plaque-specific protein directly involved in the disease process. A key study demonstrated that nearly half the patients with documented coronary events had LDL cholesterol readings within healthy range, exposing a major weakness in the standard lipid panel and the need for measuring oxidized LDL levels.

Shiel Medical Laboratory’s Oxidized LDL Triple Marker Test is the only blood test that measures oxidized LDL, which reflects atherosclerotic disease activity in the arterial wall. As an identifier of clinical and subclinical CAD, the test is superior to any other laboratory test available to assess patient risk of cardiovascular disease, which kills 400,000 Americans annually and costs $110 billion in medical services and lost productivity.

“Research studies show measuring LDL cholesterol alone is insufficient to determine whether a patient is at risk for heart attack or stroke,” said Shiel Medical Laboratory Technical Services Director, Harold M. Bates, Ph.D., who was involved in the commercial development of the oxidized LDL test. “Oxidized LDL as a biomarker test could easily become the successor to the regular LDL test because of its greater clinical efficacy.”

Shiel’s Oxidized LDL Triple Marker Test overcomes the weaknesses of conventional lipid tests by measuring oxidized LDL, a plaque-specific protein. Oxidized LDL is the atherogenic form of LDL cholesterol linked to the deposition of plaque in the artery walls. The CAD disease process depends on the oxidation of LDL, making oxidized LDL the primary culprit molecule in cardiovascular disease.

In addition to oxidized LDL, the Oxidized LDL Triple Marker Test measures two additional biomarkers linked to CAD: HDL cholesterol, an anti-atherogenic substance that inhibits the disease-causing action of oxidized LDL; and high-sensitivity C-reactive protein (hs-CRP), an independent biomarker that at certain lower levels is associated with cardiovascular disease.

Like oxidized LDL, hs-CRP is not included in the standard lipid panel even though elevated oxidized LDL and chronically elevated hs-CRP may explain why half of all patients hospitalized with CAD have lipid readings that appear normal.(1)

In published medical studies assessing known and emerging lipid biomarkers, oxidized LDL measurements rendered the most accurate snapshot of CAD risk. A 2006 study of 921 subjects, including 490 CAD patients and 431 healthy individuals in the control group, compared the relative potency of oxidized LDL to LDL cholesterol in identifying patients with CAD.(2 )Oxidized LDL showed a six-fold ability over LDL cholesterol in indicating disease. Measuring the oxidized LDL/HDL ratio and adding hs-CRP levels to round out the Triple Marker profile produced a 16-fold ability over LDL cholesterol in identifying CAD disease.

“Every physician needs to know that standard lipid panels do not measure elevated oxidized LDL even in patients with low to moderate LDL. I’m certain more patients would request the Oxidized LDL test if they knew how much more effective it is in detecting CAD than the standard LDL test,” said Charles Mitgang, M.D., an internist in Rockville Centre, N.Y. “The test has become part of my routine in identifying, treating and monitoring patients who are at risk for CAD.”

Shiel Medical Laboratory is the first and only laboratory to develop the automated Oxidized LDL Test and establish reference ranges allowing physicians to better interpret results. Shiel introduced the test in 2006, following lab validation and approval by the New York State Department of Health. The laboratory exhibits annually at Scientific Sessions for the American Heart Association and the American College of Cardiology and researchers and clinicians have embraced this lipid biomarker test as a much-needed addition to the cardiac disease prevention arsenal.

Source: PR Newswire