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Despite FDA s AmpliChip Ruling, Tiny CYP450 Shop Lives on Service to MDs

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Can a tiny company in a New Jersey suburb give Roche Diagnostics and Affymetrix — or any other company trying to sell cytochrome P450 tests — a run for their money?

In the wake of the US Food and Drug Administration’s decision not to allow the Swiss diagnostic giant to market its Affy-made AmpliChip as an analyte-specific reagent in the United States [see 11/6/03 SNPtech Pharmacogenomics Reporter], the answer just may be yes.

While the FDA’s decision may have thrown water on the future of some RNA-based drug metabolism tests currently being developed, it hasn’t stopped closely held Seryx. The Cherry Hill, NJ-based company is betting that enough health-care providers have heard about CYP450 mutations that it can make money selling CYP450 genotyping services direct to physicians without first obtaining regulatory clearance.

“There’s clearly a market for this, and we’ve been able to tap into it,” CEO Fred Mannausau told SNPtech Pharmacogenomics Reporter. Mutation-based metabolism research “is a science that’s been around awhile, but has not been put into clinical use in the physician’s office to any great extent. Our mission is to bring the science in a usable form to physicians,” he said.

Trouble is, pharmacogenomics researchers differ on their definition of what constitutes a “usable form,” so the clinical utility of CYP450 data remain “iffy,” as one academic researcher put it. In fact, it appears that only the FDA has a firm opinion of the mutations.

Despite the clinical or regulatory question marks, many pharmaceutical companies have recognized the emerging significance of the metabolism gene family and, to some extent, shops like Seryx: If physicians are using their services to help them decide when to prescribe one drug over another, drug makers want to know about it.

Seryx has a very simple business plan: Through its Signature Genetics business, it collects blood samples from patients, sends them to a lab in Germany to be genotyped for the CYP450 mutations, and returns to physicians a breakdown of which drugs their patients will likely metabolize slowly or rapidly.

Based on the genotypic results, physicians are “indicated” either to reduce or increase drug dosage, or to look for an alternate therapeutic.

Mannausau said Signature Genetics relies on data “from the medical literature” that detail what effects CYP450 mutations can have on the pharmacokinetics of approximately 150 drugs. However, he said the company’s customers have so far been mostly psychiatrists, and therefore only around 20 of the 150 drugs have been cited.

The German reference lab, Epidauros, extracts and genotypes patient DNA using home-brew methodologies, Mannausau said. He said Seryx chose the Bernried-based company over larger US reference labs because it “look[s] at more genes for us than one would find with [companies] like Quest; [Epidauros] looks at more of the alleles.”

Mannausau explained: “Out of the combination of that knowledge base and the actual genotyping from the lab, as well as knowing what drugs the patient is [currently] on, we then prepare a report specific to the patient,” he said. The report “talks about in great detail” the patient’s current treatment regimen as well as “a general roadmap” for the full 150 drugs. This takes around four weeks, Mannausau said.

Seryx employs around 30 people in New York, New Jersey, and Montreal. It’s services are sold in the United States, parts of Europe, and Asia, Mannausau said. Though he declined to say how many customers Seryx has, or what the company charges its customers, Mannausau did say that Signature Genetics has been offering these services for around one year.

Mannausau said the company currently “targets three or four” specialties for its services. He said psychiatrists are among this group because a substantial number of psychiatric drugs are affected by the 2D6 family of CYP450 mutations. Plus, he said, “psychiatrists are generally more educated in pharmacogenetics than [doctors from] other medical disciplines.” Additionally, since the service “is a … predictive and preventive type of medical practice,” Signature Genetics is marketed to to executive health programs, Mannausau said.

Other marketing efforts have led Seryx to Baylor Health Network, which is Baylor University’s health-provider network in Dallas — not Baylor University or the medical college itself, Mannausau stressed. He said Signature Genetics “has been blessed by their board,” and the company is currently “educating individual physicians and doing testing” for the health service.

As far as reimbursement goes, Mannausau said some payors will reimburse for the tests, but stressed that they review each patient on a case-by-case basis. “We have insurance codes, but it is not a standard reimbursement thing,” he said. “You need to go to an insurance company and get prior authorization.”

One potential obstacles standing in the way of broader application of CYP450-based metabolism tests is that it remains difficult to use genotypic or gene-expression data to accurately predict which patients will be slow-metabolizers or super-metabolizers.

It is estimated that one-third of Asian patients, one-third of the African Americans, and one-third of certain Hispanics are believed to be slow-metabolizers, according to Michael Smith, a researcher and physician at UCLA’s department of psychiatry.

The super-fast metabolizers, on the other hand, are “understudied,” so data will be far less robust, said Smith. For instance, it is believed that between 3 and 5 percent of American Caucasians to 10 percent of Spaniards, 20 percent of Saudi Arabians, and 30 percent of Ethiopians in state-run hospitals in California are categorized as “treatment resistant” or “non-compliant,” said Smith. “In fact, they’re actually more likely to be these super-fast metabolizers,” he said.

Asked if, as a practicing psychiatrist, he would genotype his patients for these mutations, Smith, whose lab performs its own CYP450 assays using Amersham Biosciences' CodeLink chips, said: "Only after I have an adverse event, or after I give them a medication that should cause a side effect, but doesn’t."

Others were less enthusiastic about the clinical utility of services like Signature Genetics. Jeffrey Moe, senior director of business development for the Health Sector Management program at the Duke University Fuqua School of Business, said that the science of CYP450 genotyping or expression profiling is still too young for physicians to derive any clear guidance from them.

“If a physician is offered a CYP450 test versus a low dose of [blood-thinning drug] Coumadin, which is often cited with adverse events, far and away they would prefer to use Coumadin,” Moe told SNPtech Pharmacogenomics Reporter. “Why? Because it doesn't require a significant change in the flow of their practice or the way they do medicine, and they’re not having to interpret difficult pharmacogenomic data that they may not be quite clear exactly what it means.” [Read the complete interview on page 5]

He added: “We haven’t even gotten into the economics of these kinds of tests. Let’s say that the cost of a P450 test is $300. Over time, if I’m only looking for ... less than 20 percent of the population that has this defect, is that cost effective? I think a physician would say, ‘I don't think it is. It’s easier and safer, if you will, for me to just use low-dose Warfarin.’”

— KL

 

 

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