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Pathway Launches Tropism Assay, Touts Low Cost, Fast Results, Higher Sensitivity

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With the national launch of its SensiTrop co-receptor tropism assay, Pathway Diagnostics is taking on competing cell-based and sequencing assays, promising increased sensitivity and a lower price.
 
Pathway announced this week the nationwide availability of SensiTrop, a molecular heteroduplex tracking assay that has been demonstrated to be “highly sensitive in detecting CXCR4-tropic HIV in patient samples that contain as little as 1 percent CXCR4,” the company said in a statement.
 
The tropism testing market will likely heat up now after the US Food and Drug Administration recently approved Pfizer’s CCR5 co-receptor-blocking anti-retroviral Selzentry. The label for the drug, also called maraviroc, states tropism testing and treatment history should guide treatment with the drug [see PGx Reporter 08-08-2007].
 
Pfizer used Monogram’s Trofile assay to determine whether an individual’s virus exclusively uses the CCR5 co-receptor (R5-tropic) and thus should be enrolled in maraviroc clinical trials. Monogram has called its cell-based infectivity assay the “gold standard” for the academic, clinical, government, and industrial science community. The assay certainly has more clinical trial experience, having been used in all FDA trials for CCR5 antagonist.
 
In launching its test, Pathway focused on three points — higher CXCR4 sensitivity, lower cost, and faster turnaround time — to bolster the prospects for its own assay, which Mayo Medical Laboratories has been offering since the end of August.
 
Pathway said it has demonstrated through three independent validation studies that its assay can detect CXCR4-tropic HIV when it is present at 1 percent in a mixture of both CXCR4 and CCR5 HIV. “Sensitivity is key for this assay since slightly more than 50 percent of the patients failed in the maraviroc studies, because the existing cell-based assay was unable to detect CXCR4,” Terry Robins, Pathway VP of R&D, told Pharmacogenomics Reporter this week.
 
The company plans to price its test at a 40 percent discount to Trofile’s list price. Additionally, Pathway noted that results for its assay can be available in four to seven days.
 
Direct vs. Indirect Measure
 
Pathway’s SensiTrop is a molecular diagnostic based on a technique called heteroduplex tracking, developed by Barbara Weiser and Harold Burger at the New York State Department of Health’s Wadsworth Center in Albany. The technology interrogates the V3 loop and differentiates whether an HIV virus utilizes the CXCR4 or the CCR5 co-receptors.
 
“The determination of whether the HIV from the patient uses either the CXCR4 or the CCR5 or both the CXCR4/CCR5 co-receptors is based on the detection of heteroduplex DNA hybrids formed between the patient HIV sequence and fluorescently labeled CCR5 DNA probes,” Robins said in an e-mail.
 
According to Pfizer, between 80 percent and 85 percent of treatment-naive HIV patients and about half of the treatment-experienced population are CCR5-tropic and are eligible for treatment with maraviroc. However, tropism detection is complicated by the minority of patients whose HIV is CXCR4-tropic.
 
Based on internal comparative data, SensiTrop’s ability to detect CXCR4 represents a 10-fold increase in sensitivity over existing cell-based and sequencing based methodologies, Pathway officials said.
 
In comparison, Pfizer claims that the Trofile assay can detect a 10-percent minority population of CXCR4-using HIV clones with 100-percent sensitivity, while 5 percent of the CXCR4-using population can be detected with 83-percent sensitivity. The assay can reliably determine patients’ tropism status with up to 1,000 copies of HIV-1 RNA/mL for amplification.
 
In an e-mail to Pharmacogenomics Reporter, a Monogram spokesperson characterized the two assays as “fundamentally different,” noting that Pathway’s product only “predicts tropism.”
 
“Trofile directly measures tropism [and] the positive and negative predictive value for maraviroc patient selection were demonstrated in Pfizer’s clinical trials,” the spokesperson said. “The SensiTrop assay is a gene-based sequence hybridization assay that predicts tropism based on V3 sequence hybridization patterns. There are no data demonstrating this assay's ability to identify patients that will respond to maraviroc.”
 
There is no head-to-head comparative data for Trofile and SensiTrop. However, Monogram said that based on V3 sequence diversity and the limited number of probes used in SensiTrop, “our expectation is that the assay will have reduced sensitivity to predict CXCR4 use and specificity to predict CCR5 use when compared to Trofile results. Further, our expectation is that it will perform no better and perhaps inferior to sequencing.”
 
Trofile already has established a record for the reliability of its test having been used for patient selection in all FDA trials of CCR5 antagonists. “The Pathway test has been used in none,” Monogram’s spokesperson said.
 
Pathway officials said they could not answer questions regarding SensiTrop’s performance in clinical trials for CCR5 antagonists “due to client confidentiality.”
 
Taking on Pfizer
 
Pfizer relied on Monogram’s Trofile in maraviroc’s clinical trials, but the assay is not without its flaws. Trofile’s ability to detect the minority of CXCR4 patients has been a point of concern and debate. Clinical trials have shown that the test may not detect some proportion of patients who use CCR5 and CXCR4 co-receptors and therefore will not benefit from the drug.
 

“Sensitivity is key for this assay since slightly more than 50 percent of the patients failed in the maraviroc studies, because the existing cell-based assay was unable to detect CXCR4.”

Additionally, during an FDA advisory committee meeting in May, members felt patients who stop responding to maraviroc due to resistance or co-receptor switching may need to be periodically tested with Trofile. Priced at $1,960, this is an expensive proposition, and may deter test adoption, committee members noted [see PGx Reporter 05-02-2007].
 
During the meeting, the FDA also noted it will take two to three weeks for Monogram’s labs to turn around Trofile results, another possible barrier to test adoption.
 
In entering the tropism testing market at this time, Pathway is taking on not only Monogram, but its deep-pocketed development and marketing partner Pfizer.
 
Pfizer and Monogram in May 2006 announced a non-exclusive collaboration to make Monogram’s Trofile assay available for patients worldwide. Pfizer at the time also invested $25 million in Monogram [see PGx Reporter 05-10-2006]. Selzentry is also part of an expanded access program in over 30 countries, where Pfizer has been providing the drug until it receives regulatory approval. Outside the US, Pfizer will market Trofile.
 
In the US, Pfizer and Monogram have their own sales forces for marketing the drug and diagnostic separately. However, Pfizer’s reps will be equipped with an information sheet on the Trofile assay and be able to point physicians to Selzentry’s label to highlight the need to establish the tropism status for patients prior to maraviroc treatment.
 
In terms of cost, Monogram’s spokesperson noted that patients will likely not pay $1,960 for testing, as reimbursement by payers is expected. Medicare has already said that the test will be covered. The company recently announced that the California-based CMS contractor National Heritage Insurance Company will pay for the test.
 
“We are working with all major public (Medicaid) and private payers to expand coverage to all patients,” Monogram’s spokesperson added.
 
Pathway, in comparison, is still in the early stages of its marketing and reimbursement efforts. Company officials said it is perhaps too soon to discuss the reimbursement prospects for the assay. However, since Pathway will try to differentiate the assay in the marketplace as a more cost-effective solution compared to other HIV tropism tests due to its sensitivity, rapid turnaround time and lower price, the company is hoping insurers will want to cover the test.
 
“We look at this based on the cost to healthcare,” Pathway President and CEO Wally Narajowski told Pharmacogenomics Reporter this week. “Given the fact that the list price is 40 percent less than currently available assays, the ultimate cost to providers, payors, and patients should be less.”
 
Pathway officials described the company’s business model as one in which the company licenses its biomarker IP, develops the technology, and commercializes it through partnerships with in vitro diagnostics companies and commercial labs.
 

“Pathway will support [these companies and commercial labs] in their commercialization efforts with technology and assay performance information, scientific publications and speaking engagements targeted to physicians that treat HIV-infected patients,” the company said.

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