Celera Publishes Data Extending the Association Between the KIF6 Gene Variant and Differential Reduction of Coronary Events From Statin Therapy to the Elderly With Prior Vascular Disease
Stratifying the Study According to KIF6 Status Demonstrated Increased Effectiveness of Statin Therapy in KIF6 Carriers: the Number Needed to Treat to Prevent One CHD Event was 16 in Carriers Compared With 83 in Noncarriers
KIF6 Has Been Associated With Differential Reduction of Coronary Events From Statin Therapy in 4 Prospective Randomized Double Blind Clinical Trials and With Risk of Coronary Events in 5 Prospective Cohorts
ALAMEDA, Calif.--(BUSINESS WIRE)--Mar 24, 2010 - Celera Corporation (NASDAQ:CRA) today announced the publication of data reporting that elderly (over age 70) carriers of the KIF6 gene variant with prior vascular disease received significant benefit from pravastatin (Pravachol®) therapy. Previous research has shown that a variant of the KIF6 gene, a member of the molecular motor protein kinesin family, is associated with up to a 55% increased risk of primary and recurrent coronary heart disease (CHD) events in the placebo arms of the clinical trials, and that this increased risk is virtually eliminated with statin therapy. This paper has been published ahead of print in the European Journal of Cardiovascular Prevention and Rehabilitation, and is currently available on the publication's website at: http://journals.lww.com/ejcpr/Abstract/publishahead/KIF6_Trp719Arg_polymorphism_and_the_effect_of.99827.aspx
The effect of pravastatin versus placebo on coronary events according to KIF6 carrier status was investigated among 5,752 patients of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. A key finding of the study was that in 2,542 subjects with prior vascular disease, pravastatin therapy significantly reduced coronary events in KIF6 carriers but not in noncarriers: absolute risk reduction was 6.3% in carriers versus 1.2% in noncarriers. The study showed that the number needed to treat (NNT) with pravastatin to prevent one CHD event was 16 in KIF6 carriers and 83 in noncarriers. The original reports of the PROSPER study indicated that only the elderly with prior vascular disease received substantial and significant reduction of events from pravastatin therapy. The differential reduction of CHD events between KIF6 carriers and noncarriers in PROSPER patients with prior vascular disease was observed despite the same on-therapy lipid levels observed in carriers and noncarriers.
“We're pleased to have replicated our findings for KIF6 in this important segment of the population as it provides additional information to help physicians identify those elderly patients with prior vascular disease in whom statins work particularly well,” said Kathy Ordoñez, Chief Executive Officer of Celera.
Celera is pursuing regulatory registration for a diagnostic product based on research findings pertaining to KIF6.
About the PROSPER study
The study population was derived from PROSPER, a randomized, double-blind, placebo-controlled trial designed to assess the effect of pravastatin for the prevention of major cardiovascular events among participants aged at least 70 years at enrollment who were at risk for cardiovascular events because of preexisting vascular disease, smoking, hypertension, or diabetes. 5,804 patients (2,804 men and 3,000 women) were randomized to treatment with 40 mg pravastatin per day or placebo in three centers (Cork, Ireland; Glasgow, Scotland; and Leiden, The Netherlands) and followed for an average of 3.2 years; 44.2% of the enrolled patients had a history of prior vascular disease (myocardial infarction, stable angina, intermittent claudication, stroke, transient ischemic attacks, arterial surgery, or amputation for vascular disease more than 6 months before study entry).
The end point of this genetic study of PROSPER was time from enrollment to the first incident coronary event, a composite of coronary heart disease death, nonfatal myocardial infarction, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft. This genetic study was able to evaluate 5,752 of the 5,804 patients enrolled in PROSPER.
The PROSPER study was led by Professors James Shepherd and Ian Ford at the University of Glasgow and Royal Infirmary, Glasgow, United Kingdom; Professor Wouter Jukema from University of Leiden, The Netherlands; and Professor Michael Murphy University College Cork, Ireland. Olga A. Iakoubova, M.D., Ph.D., Principal Investigator at Celera, was the lead author of this genetic study which was conducted with collaborators at the University of Glasgow and Royal Infirmary, Glasgow, UK, Leiden University Medical Center, Leiden, The Netherlands, and University College Cork, Ireland. All statistical analysis was performed by the statistical group at the University of Glasgow.
Other research on KIF6
The KIF6 associations have been demonstrated previously in two prospective, randomized clinical trials that assessed the effect of pravastatin on the prevention of CHD events: the secondary prevention Cholesterol and Recurrent Events (CARE) study and the primary prevention West of Scotland Coronary Prevention Study (WOSCOPS). Additionally, a genetic study of PROVE IT•TIMI 22 reported that in patients after an acute coronary syndrome (ACS), high-dose atorvastatin (Lipitor®), compared with standard dose pravastatin, was significantly more effective at reducing CHD events in KIF6 carriers than in noncarriers.
The KIF6 gene variant was previously reported to predict risk of CHD in other prospective studies. This gene variant was associated with increased risk of CHD in Caucasian and African American participants of the Atherosclerosis Risk in Communities (ARIC) study (a study of 12,556 middle aged Americans), and with increased risk for myocardial infarction (MI) in both the Cardiovascular Health Study (a study of 4,552 Americans, aged 65 or older), and the Women's Health Study (a study of 25,283 women older than 45 years without a previous history of CHD). Thus, this KIF6 gene variant has been associated with CHD risk in studies including a total of approximately 55,000 people.
The increased risk of CHD events observed in KIF6 carriers has been shown to be independent of other well-known CHD risk factors, including smoking, hypertension, cholesterol level, age and sex, further supporting the conclusion that the KIF6 gene variant is an independent predictor of risk for CHD. To date, the benefits of statin therapy for KIF6 carriers has only been studied with atorvastatin and pravastatin therapy.
In a case-control analysis of subjects in the Ottawa Heart Study, no association was found between KIF6 and arteriographic evidence for a >50% coronary artery narrowing, which is a different clinical endpoint than the CHD examined in the other KIF6 studies referenced above. In this study, 89% of the cases were on statin therapy, which Celera believes may have had an effect on the lack of an association with risk in KIF6 carriers.
Celera is a healthcare business focusing on the integration of genetic testing into routine clinical care through a combination of products and services incorporating proprietary discoveries. Berkeley HeartLab, a subsidiary of Celera, offers services to predict cardiovascular disease risk and improve patient management. Celera also commercializes a wide range of molecular diagnostic products through Abbott and has licensed other relevant diagnostic technologies developed to provide personalized disease management in cancer. Information about Celera Corporation, including reports and other information filed by the company with the Securities and Exchange Commission, is available at http://www.celera.com.
Certain statements in this press release are forward-looking. These may be identified by the use of forward-looking words or phrases such as "believe," "plan," and "could," among others. These forward-looking statements are based on Celera Corporation's current expectations. The Private Securities Litigation Reform Act of 1995 provides a "safe harbor" for such forward-looking statements. In order to comply with the terms of the safe harbor, Celera notes that a variety of factors could cause actual results and experience to differ materially from the anticipated results or other expectations expressed in such forward-looking statements. These factors include but are not limited to: (1) the risks that Celera may not receive required regulatory approvals to commercialize a diagnostic product for KIF6; (2) Celera is using novel and unproven methods to discover markers for the development of new diagnostic products, which may not be successful; (3) the diagnostic industry is very competitive, and new diagnostic products may not be accepted and adopted by the market; (4) demand for diagnostic products may be adversely affected if users of these products cannot receive adequate reimbursement for these products from third party payors such as private insurance companies and government insurance plans; (5) potential product liability or other claims against Celera as a result of the testing or use of its products; and (6) uncertainty of the availability to Celera of intellectual property protection, limitations on its ability to protect trade secrets, the risk to it of infringement claims, and the possibility that it may need to license intellectual property from third parties to avoid or settle such claims. The foregoing list sets forth some, but not all, of the factors that could affect Celera's ability to achieve results described in any forward-looking statements. For additional information about the risks and uncertainties that Celera faces and a discussion of its financial statements and footnotes, see documents filed by Celera with the SEC, including its transition report on Form 10-K and all subsequent periodic reports. All information in this press release is as of the date of the release, and Celera does not undertake any duty to update this information, including any forward-looking statements, unless required by law.
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Contact: Celera Corporation
David Speechly, Ph.D., 510-749-1853
Posted: March 2010