April 19th, 2018
The CMS National Coverage Decision on NGS
New Insights: As a result of the recent CMS National Coverage Decision on NGS, the MolDX® program of Palmetto GBA® is now actively considering cover...
Epizicom, a combination of abacavir and lamivudine, both nucleoside analogue HIV-1 reverse transcriptase inhibitors, is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
The challenge: GSK drugs containing abacavir (ABC) were discovered to induce hypersensitivity in a small number of patients.
The problem: The hypersensitivity scare meant that Gilead’s Truvada, which had an issue-free launch, was able to capture 75 per cent of the market by July 2007, up from 50 per cent a year earlier.
Countries that Routinely Test have Higher ABC Market Shares
|Epzicom/Kivexa Share||ABC-Containing Products Share||% of Physicians Using Test |
The PREDICT study was designed to establish the effectiveness of prospective HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir. The data from the PREDICT study along, with other retrospective trial data, were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) and International AIDS Society meeting in June 2007, and published in the New England Journal of Medicine in February 2008.
The double-blind, prospective, randomized PREDICT study involved 1956 patients from 19 countries, who were infected with human immunodeficiency virus type 1 and who had not previously received abacavir. The team randomly assigned patients to undergo prospective HLA-B*5701 screening, with exclusion of HLA-B*5701–positive patients from abacavir treatment (prospective-screening group), or to undergo a standard-of-care approach of abacavir use without prospective HLA-B*5701 screening (control group). All patients who started abacavir were observed for six weeks. The team performed epicutaneous patch testing with the use of abacavir.
The trial found that the HLA-B*5701 allele was present in 5.6 per cent of patients (109 of 1956 patients). Of the patients receiving abacavir, 72 per cent were men, 84 per cent were white, and 18 per cent had not previously received antiretroviral therapy. Screening eliminated immunologically-confirmed hypersensitivity reaction (0 per cent in the prospective-screening group versus 2.7 per cent in the control group, P<0.001), with a negative predictive value of 100 per cent and a positive predictive value of 47.9 per cent. The hypersensitivity reaction was clinically diagnosed in 93 patients, with a significantly lower incidence in the prospective-screening group (3.4 per cent) than in the control group (7.8 per cent).
The study concluded that HLA-B*5701 screening reduced the risk of a hypersensitivity reaction to abacavir. It showed that in populations similar to the predominantly white group in the study, 94 per cent of patients do not carry the HLA-B*5701 allele and are at low risk for hypersensitivity reaction to abacavir.
Ultimately, the study showed that a pharmacogenetic test can be used to prevent a specific toxic effect from a drug.
To demonstrate unequivocally the role of the test in eliminating the abacavir hypersensitivity problem, GSK initiated a prospective study in 2006, the results of which were published in the New England Journal of Medicine in February 2008.
GSK launched a major marketing offensive in August 2007, recommending that all HIV patients be tested.
FDA Approves Updated Prescribing Information for Abacavir (Ziagen, Epzicom and Trizivir)
This week GlaxoSmithKline (GSK) and the US Food and Drug Administration (FDA) announced new updated label information for the nucleoside reverse transcriptase inhibitor abacavir (Ziagen). Abacavir is also a component of the fixed-dose combination pills Epzicom (abacavir + lamivudine [3TC]) and Trizivir (abacavir + lamivudine + Zidovudine [AZT]).
To enable the promotion of the HLA-B*5701 test, which was not FDA-approved, GSK agreed with the FDA that it would be incorporated into the black box warnings for drugs containing abacavir.
The demand for testing grew rapidly in the US after the campaign was launched and Epzicom's revenue growth resumed after a 4-6 month hiatus.
GSK also used the diagnostic market to turn a defensive strategy into an offensive strategy against Epzicom’s nearest competitor, Tenofovir, which had long-term toxicity issues not previously focused on by physicians.