This article has been updated to note that the KIF6 test being submitted for regulatory approval is called the KIF6 Genotyping Assay, and not StatinCheck, which is the LDT-version of the test.
Originally published Jan. 3.
Celera this week filed a premarket approval application with the US Food and Drug Administration for its KIF6 StatinCheck genotyping test, an in vitro diagnostic for gauging the risk of coronary heart disease and statin benefit.
The announcement that the company is moving ahead with its plans to launch an FDA-approved KIF6 test in the US follows the publication of a hotly contested study that recently shed doubt on the clinical utility of the KIF6 gene marker (PGx Reporter 10/13/10).
The KIF6 Genotyping Assay, which will run on Abbott's m2000 platform, detects a variant in the KIF6 gene. Ahead of FDA approval of a KIF6 test kit, Celera's Berkeley HeartLab is offering KIF6 assessment services through its laboratory.
In October, however, the publication of a large study in the Journal of the American College of Cardiology reported no significant associations between the KIF6 gene, the risk of coronary disease, and response to statins. The study, led by Themistocles Assimes of Stanford University, investigated the association between the KIF6 Trp719Arg allele and the development of coronary artery disease in more than 17,000 CAD patients and more than 39,000 controls from 19 different studies conducted globally, and failed to find any association between the allele and CAD.
This "puts the nail in the coffin” for KIF6 as a marker for gauging risk of coronary disease, Tom Quertermous, a professor in cardiovascular medicine at Stanford and the study’s senior author, said in a statement following the publication of the study. “This is such a big study — if there was a significant association between this variant and coronary disease, we would have found it.”
However, Celera disagreed with this assessment, criticizing the study as containing "numerous inaccuracies, misstatements, and omissions." The company takes issue with the JACC meta-analysis in that the studies did not have reliable information on the use of statins and patient cohorts involved non-fatal cases of CAD.
Celera claims it has validated the 719Arg allele link to a reduction in risk of coronary heart disease in a combined analysis of seven large prospective studies, and has proven the association between KIF6 and statin benefit through retrospective analysis of four prospective randomized-controlled trials: the secondary prevention Cholesterol and Recurrent Events (CARE) study; the primary prevention West of Scotland Coronary Prevention Study (WOSCOPS); the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study; and Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE IT―TIMI 22).
In total, Celera claims that the KIF6 association to coronary heart disease and statin benefit have been validated in approximately 55,000 people, showing that carriers of the KIF6 polymorphism have between a 22 percent and 55 percent greater risk for cardiac events than non-carriers.
Additionally, Celera is working with pharmacy-benefit manager Medco to build the clinical utility evidence in support of KIF6 testing. Last year, Medco and Celera launched a prospective, randomized study to evaluate whether patients' knowledge of their KIF6 gene variant status increases their adherence to statin therapy compared to those not offered the test (PGx Reporter 09/23/09).
The negative study results published in the JACC haven't stopped Celera from embarking on a global commercialization strategy for the KIF6 test. Approximately 180 million people are estimated to be carriers of the KIF6 variant worldwide.
Six months before filing for regulatory approval with the FDA, Celera applied the CE Mark to the test for selling it in the European Union and other countries. Then, in September, Celera granted Abbott a license to exclusively distribute the KIF6 test for use on the m2000 instrument system in countries that recognize the CE Mark. In the US, Celera is selling the test with an internal sales team of 23 reps. Celera also has deals with external labs in Europe and in the US to sell the test.
The company said that more than 870 of Abbott's m2000 systems have been placed in laboratories worldwide. Earlier this year, Celera CEO Kathy Ordonez said that its subsidiary Berkeley HeartLab has performed nearly 200,000 KIF6 tests since the company launched a laboratory-developed test, StatinCheck, in the US two years ago.