Third Wave Technologies (TWT; Madison, Wisconsin) said the FDA has cleared the company's Invader UGT1A1 molecular assay for in vitro diagnostic use, making it the first pharmacogenetic test to be approved by the FDA for use as a companion diagnostic to a specific drug therapy.

The drug is Camptosar, a chemotherapy product used to treat colorectal cancer.

The FDA, which one analyst said was the motivator behind the test, said the test "will help doctors make personalized drug treatment decisions for some patients," joining what the agency called "a growing list of genetic tests used by physicians to personalize treatment decisions."

"Doctors can use this information to help determine the right drug dosage for individual patients, and minimize harmful drug reactions," the FDA said.

The Invader UGT1A1 test is cleared for use to identify patients who may be at increased risk of adverse reaction to the chemotherapy drug Camptosar (irinotecan) by detecting and identifying specific mutations in the UGT1A1 gene that have been associated with that risk, the company said.

Camptosar was relabeled recently to include dosing recommendations based on a patient's genetic profile.

"The selection of the right dose is one of the greatest challenges in the treatment of cancer patients," said Dr. Howard McLeod, professor of oncology at Washington University School of Medicine (St. Louis). "The recent expansion of available therapies for colorectal cancer has made toxicity avoidance an important aspect of the clinical decision."

About 150,000 new cases of colorectal cancer are diagnosed each year in the U.S., the company said.

Third Wave also said that its UGT1A1 molecular diagnostic test is built on the company's Invader chemistry. In a study submitted to the FDA as part of its application for clearance by the agency, the Invader UGT1A1 molecular assay was 100% accurate compared to DNA sequencing.

The FDA said that the "Invader assay detects variations in a gene called UGT1A1 that produces the enzyme UDP-glucuronosyltransferase. That enzyme is active in the metabolism of certain drugs, such as irinotecan .... variations in the UGT1A1 gene can influence a patient's ability to break down irinotecan, which can lead to increased blood levels of the drug and a higher risk of side effects."

The FDA said the Invader assay was studied in 66 patients. That study showed that people with one type of genetic variation have a five times greater risk of experiencing irinotecan toxicity.

"While the pharmacogenetic market is just beginning to emerge, we believe it will become increasingly valuable," said John Puissis, president and CEO of Third Wave, in a statement. "Our goal is to ensure that Third Wave is well positioned to capture that value as the market develops and molecular diagnostic and drug pairings continue to be identified, as we expect they will be."

The FDA said that the Invader now joins tests such as Roche Diagnostics' (Indianapolis) AmpliChip, which is used to "individualize dosage of antidepressants, antipsychotics, beta-blockers and some chemotherapy drugs," the FDA said.

Roche reported its FDA clearance in January. That test, which uses Affymetrix's (Santa Clara, California) microarray technology, analyzes a patient's Cytochrome P450 2D6 and 2C19 genotypes from genomic DNA extracted from a blood sample. Roche said at the time that test results will allow physicians to consider unique genetic information from patients in selecting medications and doses of medications for a variety of conditions such as cardiac diseases, pain and cancer.

Roche said that the multiple variations in the CYP2D6 gene can result in poor, intermediate, extensive, or ultra-rapid metabolism of CYP2D6-dependent drugs from a variety of classes, not only including antidepressants and antipsychotics, but also anti-arrhythmics, beta-blockers, pain medications, anti-emetics and some anticancer drugs.

Another test is the TruGene HIV-1 Genotyping Kit and OpenGene DNA Sequencing System by Visible Genetics (Toronto), which was FDA-cleared in September 2001. The kit was the company's first FDA-approved product and was considered a major advancement in the treatment of AIDS patients.

That kit works by genetically decoding the highly mutagenic HIV-1 from patient serum, then identifying mutations in the virus by comparing the genome to a control, ultimately providing a personalized treatment regimen.

Pacific Growth Equities (San Francisco) senior analyst Adam Chazan said, "This really is a first," because it's a specific test tied to a specific drug. He also said the test was "motivated by the FDA," which in studies had found that of colorectal cancer patients, about "10% or so are at risk of severe adverse reactions" from irinotecan.

"By genotyping them, in essence, you can basically figure out who those bad actors are and either get [patients] on a different drug, change the dosage or monitor them, and that is something that effectively gets you to personalized medicine where patients are getting the right drug at the right time and the right dose."

Chazan said this is the company's first FDA-cleared test, so the clearance validates its technology and "regulatory machinery."

"That in and of itself is important," he said. "But specifically what it does is it tees up this whole personalized medicine [approach] where you've got drugs and their companion diagnostics."

No Comments