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LabCorp May Benefit in HLA-Dx Space from FDA’s Call for Gene Data in Abacavir Label

Laboratory Corporation of America is well-positioned to lead the human leukocyte antigen-testing market since the US Food and Drug Administration advised healthcare professionals to genetically screen all HIV patients for the HLA-B*5701 allele before initiating treatment with the drug abacavir.  
“Genetic tests for HLA-B*5701 are available and all patients should be screened for the HLA-B*5701 allele before starting or restarting treatment with abacavir or abacavir-containing medications,” the FDA said in a letter to providers issued last week.
The agency also asked makers of the nucleoside analog reverse transcriptase inhibitor to update the drug’s label to include information about the increased risk of fatal hypersensitivity reaction in HIV patients who have the HLA-B*5701 allele.
The new boxed warning in the abacavir label states that “patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir,” and advises healthcare officials to “discontinue [abacavir] as soon as a hypersensitivity reaction is suspected.” 
The FDA defines hypersensitivity reactions as a serious and sometimes fatal “multi-organ syndrome” that manifests when abacavir-treated patients exhibit two or more of the following clinical signs: fever, rash, gastrointestinal symptoms, respiratory symptoms, and constitutional symptoms.
“Regardless of HLA-B*5701 status, permanently discontinue [abacavir] if hypersensitivity cannot be ruled out, even when other diagnoses are possible,” the new label reads.
The updated labeling is the latest effort by the FDA to include pharmacogenomic information in drug package inserts.
Last August, the FDA asked makers of the anticoagulant warfarin to include information about the increased risk of adverse events among patients who carry CYP2D6 and VKORC1 genetic variants. 
Yet despite the FDA’s regulatory action, the uptake of warfarin genetic testing has been slow. According to diagnostic test makers, warfarin testing did not receive the necessary bump from the FDA since the agency only provided information explaining how genotypes may impact response to the drug and not a recommendation for genetic testing. On the other hand, many insurers still do not reimburse for the test, noting that the clinical utility of warfarin genetic testing has yet to be proven [see PGx Reporter 09-05-2007, 12-19-2007].
Even before the labeling update for warfarin, in 2005, the FDA amended the label for the colorectal cancer drug irinotecan, asking physicians to screen all patients to see if they were homozygous for the UGT1A1*28 allele, and if so, start them on a lower dose of the drug.

“We were the first commercial laboratory to introduce the test for the HLA-B*5701 mutation that identifies hypersensitivity to the abacavir AIDS treatment drug.”

Comparatively, abacavir’s re-labeling is closer to that of irinotecan, since the FDA has recommended that all patients “should be screened” for the HLA-B*5701 allele before taking the drug. 
The agency noted that it updated the label after reviewing data from two studies that recommend pre-therapy HLA-B*5701 screening.
One of these studies was a genome-wide association study, published in the New England Journal of Medicine, in which GlaxoSmithKline researchers demonstrated “sufficient statistical power to permit the identification of strong genetic predictors of [adverse drug reaction] risk in a prospective manner with modest numbers of ADR cases.” 
The branded version drug, manufactured by GSK, is called Ziagen.
GSK researchers used LabCorp’s PCR-based HLA-B*5701 test to genetically screen patients in the study. Furthermore, LabCorp began offering HLA-B*5701 screening three years ago, which gives the company a significant lead in the market against competitors that might arise in response to the labeling update.
“Other laboratories may have begun their first HLA test by offering this test, but no one has LabCorp's expertise or experience,” LabCorp Chief Medical Officer Myla Lai-Goldman told Pharmacogenomics Reporter this week.
Although the company began specifically offering HLA-B*5701 screening in 2005, LabCorp has been performing HLA molecular testing since 1991 and has performed HLA genotyping for the National Marrow Donor Program since 1992.
Furthermore, Lai-Goldman noted that she and another LabCorp scientist, Hawazin Faruki, have two articles on HLA-B*5701 screening, one in Pharmacogenetics & Genomics in October 2007, and another in Future Medicine in May 2008. Lai-Goldman and Faruki are in the process of completing a third article on HLA-B*5701 screening.
“In companion diagnostics, we led by introducing HIV viral load followed with HIV and HCV genotyping,” LabCorp CEO David King said last week during the firm’s second-quarter conference call with investors (see related story, in this issue). “We were the first commercial laboratory to introduce the test for the HLA-B*5701 mutation that identifies hypersensitivity to the abacavir AIDS treatment drug.”
Although LabCorp doesn’t break out sales figures for its individual test offerings, Allen Roses, GSK’s former head of genetics research, previously told Pharmacogenomics Reporter that following the presentation of data from GSK’s genome-wide association study at an AIDS conference last summer, LabCorp saw a nine-fold increase in the sales of its HLA-B*5701 test by the end of 2007 [see PGx Reporter 03-26-2008].
According to Roses, who was also one of the authors of the study published in the NEJM, although uptake of LabCorp’s test was slow when it first launched, the new prospective data provided a significant boost for the test. Abacavir’s experience could be a lesson for warfarin testing, Roses suggested. 
“If you can compare this with the … diagnostics for [warfarin] — the doctors think they don’t need the test, that they can handle dosing patients without the test — for whatever reason, the uptake has been minimal at best,” Roses noted.
“This [test for hypersensitivity to abacavir] is inexpensive, and the uptake has been dramatic … from the point of view of diagnostic testing,” he said. “And it’s been below the radar. It wasn’t done through newspapers, it wasn’t done through press. It was done by sheer science.”
Lai-Goldman said that most of the orders for the HLA-B*5701 test are coming from HIV practitioners and HIV clinics. However, many hospitals, academic medical centers, and other reference labs have also ordered the test from LabCorp, she noted.
“The main market for the test are abacavir-naïve, HIV-positive patients,” Lai-Goldman said. “Physicians may find it useful to have the HLA-B*5701 result available on the patient's chart so that if they decide abacavir is a good treatment option, they are aware of the patient's HLA-B*5701 status.”
According to the latest statistics from the Centers for Disease Control and Research, in the US there were 233,079 HIV-infected people as of March of this year, and 448,871 people were living with AIDS at the end of 2006. Between 5 percent and 8 percent of HIV-infected patients are HLA-B*5701 positive.
LabCorp did not reveal the cost of the test.

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