Pharmigene said last week that 50 hospitals in Taiwan will now administer its genetic test to predict adverse events in patients being considered for treatment with the anti-seizure drug carbamazepine.
Under the partnership, the hospitals will use Pharmigene's test for the human leukocyte antigen gene variant HLA-B*1502 in order to reduce incidence of carbamazepine's severe, sometimes life-threatening side effects: Stevens-Johnson syndrome and toxic epidermal necrolysis.
The test uses real-time PCR to identify the presence of the HLA-B*1502 allele, a marker for increased risk of SJS-TEN skin reactions in some Asian populations, especially Han Chinese and Thai ethnicities. In a joint effort, Pharmigene and the hospital group submitted an application to justify the need for the test to Taiwan’s national insurance payer, which gave its approval, according to Luke Chen, Pharmigene’s CEO.
“They are now covering the test one hundred percent,” Chen told PGx Reporter.
The US Food and Drug Administration updated the label for carbamazepine in 2007 to recommend that patients of Asian ancestry be tested for HLA-B*1502 before using the drug because of increased risk of SJS-TEN (PGx Reporter 12/19/2007).
Stevens-Johnson syndrome and the related toxic epidermal necrolysis are severe skin reactions characterized by fever, rapidly developing rash and blisters, and detachment of epithelial layers both externally and internally.
In a study published in the New England Journal of Medicine in March, researchers from Taiwan's Academia Sinica showed that the use of HLA-B*1502 testing to determine which patients should avoid carbamazepine treatment successfully decreased the incidence of these side effects (PGx Reporter 3/23/2011).
According to Chen, Pharmigene chose real-time PCR for its test because it is already popular, and offers ease and speed for participating hospitals. Patients who undergo the test do so because they need medication, he said, so the faster they can be tested, the faster they can begin or continue treatment.
Some of the 50 hospitals run the test in house, using Pharmigene’s PG1502 DNA Detection Kit. Others send samples to an outside lab or a larger hospital. Chen said that Pharmigene also has a gel-based test available for hospitals that do not have access to a real-time PCR instrument or to an outside lab.
Pharmigene was founded in 2005 based on technology developed at Academia Sinica related to warfarin sensitivity and other adverse drug reactions. The company has offices in Palo Alto, Calif., as well as offices and a research and a manufacturing facility in Taiwan.
The company reports more than 99 percent sensitivity and 98 percent specificity for the HLA-B*1502 test. The false positive rate is zero among Taiwanese, Han Chinese, Thai, and Vietnamese subjects, but “once you get into Indonesia and the Philippines, populations in these regions have” other alleles that contribute to false positives, Chen explained.
Generic carbamazepine is much less expensive than alternative anti-seizure treatments — about one-fifth the price of a commonly prescribed alternative, gabapentin, according to Chen. It is expected that testing for HLA-B*1502 will allow these hospitals to reap the savings of prescribing the cheaper drug, while avoiding its dangerous side effects.
The company estimated that the use of its test to selectively prescribe the lower-cost carbamazepine to patients negative for HLA-B*1502 could save Taiwan several billion dollars over the next ten years and about a billion dollars per year afterward.
“In the US, the healthcare system gives the best drug no matter the cost, but in many places, people can’t afford new drugs, and we have to make a way to maintain old drugs. If we offer a way to make them safer, that is a big step,” Chen said.
“While billions are spent in developing new drugs, we believe that billions more can be saved by extending the life of these generic drugs,” he noted in a statement.
Pharmigene is taking steps to market its test in the US and plans to file for US Food and Drug Administration approval in the future, but several factors may delay this process.
The key issue, Chen said, is the fact that the medical field has been slow to adopt pharmacogenomic approaches for preventing adverse drug reactions, limiting the use of this type of testing initially.
In addition, the market for this particular test in the US is much smaller than in Asia, where there is a higher population for whom HLA-B*1502 is a predictive marker. That fact hasn't kept companies from eyeing the market, however. Chen said that several US companies have begun offering lab-developed HLA-B*1502 tests since the FDA added its warning to carbamazepine's label in 2007.
Pharmigene’s test is also available in the US, registered with the FDA as an ASR. In 2010 the company licensed its IP for the test to the Mayo Clinic. Chen said that Mayo is evaluating the Pharmigene test against its own CLIA-validated test to see if it offers any improvements in performance, labor, or cost.
Pharmigene also plans to expand further in the Asia-Pacific region. According to Chen, the company has “very good partners in Thailand, Indonesia, Philippines, Malaysia, Singapore, and Hong Kong,” where the frequency of HLA-*1502 can be as high as 20 percent of the general population.
HLA-B*1502 is not the only strong marker for SJS-TEN of interest to Pharmigene. The company also has a test for HLA-B*5801, which is a marker for significantly increased risk of SJS-TEN in patients taking allopurinol, a common treatment for hyperuricemia. Chen said HLA-B*5810 is not limited to Asians, though it varies in frequency among different populations. This might mean a larger potential market in countries like the US.
The FDA has not added a recommendation for genetic testing to allopurinol as it has for carbamazepine.
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