23andMe has begun reporting to customers their genetic risk for being sensitive to warfarin.
"About two weeks ago, we added a report to our Health and Traits section (which now includes over 100 reports) about warfarin sensitivity," a 23andMe spokesperson told Pharmacogenomics Reporter last week over e-mail.
When customers sign up for 23andMe's $399 service over the Internet, they will now learn whether they test positive for three SNPs — VKORC1, CYP2C9 *2, and CYP2C9*3 — that are associated with an increased risk for experiencing adverse reactions to the anticoagulant warfarin.
23andMe joins DNA Direct and Decode Genetics, which offer similar DTC services for warfarin metabolism.
In addition, by offering SNP data on warfarin sensitivity, 23andMe may be gearing up to recruit participants for future research projects seeking new gene associations and the clinical utility of PGx-guided warfarin dosing. Last year, 23andMe launched its own research division called 23andWe. The first project it launched aims to study the genetic underpinnings of Parkinson's disease [see PGx Reporter 06-04-2008].
In an e-mail to Pharmacogenomics Reporter, a 23andMe spokesperson said that the company is not currently doing research on gene-guided warfarin dosing and doesn't have any research partnerships on the subject. "We plan to do some research in this area in the future," the spokesperson said.
At the American College of Medical Genetics' Clinical Genetics Meeting last week in Tampa, Fla., 23andMe co-founder Linda Avey said the company is hoping to eventually build a community of warfarin users, track their INRs, and develop an "evidence base" for gene-guided dosing. She also said they hope to find additional markers for response.
Approximately 2 million people are initiated on warfarin therapy each year to prevent blood clots, heart attacks, and stroke. According to the US Food and Drug Administration's adverse events reporting database, complications from warfarin are the second-most common reason for emergency room visits, behind adverse reactions from insulin.
Most consumer genomics firms maintain that the information gleaned from their services are for patient education only and not for medical decision-making. However, in offering information directly to consumers over the internet about their gene-based responses to prescription drugs, critics have questioned whether these companies are crossing the line from educating the public to influencing the practice of medicine [see PGx Reporter 08-20-2008].
As these firms are providing gene-based warfarin metabolism data to all comers, the regulatory, reimbursement, and research communities have been debating the clinical utility and cost-effectiveness of pharmacogenomics-guided warfarin dosing in the clinical setting.
Two years ago, the FDA asked manufacturers of warfarin to update warfarin's label with information explaining how genotypes may impact how patients respond to the drug [see PGx Reporter 09-05-2007].
However, given the lack of data on whether pharmacogenomics-guided warfarin dosing is clinically useful, many major insurers do not yet reimburse for such testing. While the Centers for Medicare & Medicaid are considering whether to cover the technology, one published study found that it is only cost-effective to genotype patients at high-risk for bleeding events [see PGx Reporter 08-13-2008].
"Testing everyone for SNPs in VKORC1 and CYP2C9 is unlikely to be cost effective," Brian Gage, associate professor of medicine at Washington University in St. Louis, told Pharmacogenomics Reporter this week. "I recommend testing only in patients who are new to warfarin and at high risk of hemorrhage and who will have the results available before the fourth dose."
Gage issued similar comments to CMS' national coverage determination for PGx-guided warfarin dosing. He also developed WarfarinDosing.org, a free site designed to help doctors estimate warfarin doses by applying an algorithm that uses clinical factors and patients’ genotypes.
Warfarin's label notes that the variant alleles CYP2C9*2 and CYP2C9*3 decrease a patient's ability to clear warfarin. Other CYP2C9 alleles mentioned in the label linked to reduced enzymatic activity at lower frequencies include *5, *6, and *11 alleles in those of African ancestry and *5, *9, and *11 alleles in Caucasians. With regard to VKORC1, the label highlights that the -1639G>A allele has been associated with the need to lower doses of warfarin in patients.
Recent studies have linked a third SNP, CYP4F2, to warfarin sensitivity [see PGx Reporter 03-25-2009].