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Sera Prognostics Presents Results From Validation Study of PreTRM Test

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NEW YORK (GenomeWeb) – Sera Prognostics this week announced results from the validation study of its PreTRM proteomic test for assessing the risk of preterm birth.

Detailed in a presentation at the Society for Maternal-Fetal Medicine's Annual Pregnancy Meeting in Atlanta, the Proteomic Assessment of Preterm Risk (PAPR) study found that the test was able to identify women who gave birth at or before 35 weeks gestation with an area under the receiver operating curve (AUC) of .93. It identified women who gave birth at or before 37 weeks with an AUC of .75. The addition of pregnancy and medical history variables did not improve the test's performance.

While the total cohort used in the study consisted of 5,501 patients, most of these samples were used for discovery and verification. The validation cohort used to generate the performance data presented this week consisted of a relatively small set of 18 cases and 36 controls.

Sera is now preparing for a wider launch of the PreTRM test, Gregory Critchfield, the company's chairman and CEO, told GenomeWeb.

Sera rolled out a limited commercial launch of the test this fall, making it available primarily to key opinion leaders who were working with Sera on the PAPR study, Critchfield said. The test is intended to be given at 19 weeks gestation and provides women and their doctors with their percent risk of giving preterm birth along with a comparison of their individual risk to that of the general population.

The PAPR study enrolled women at 17 to 28 weeks of gestation at 11 sites between 2011 and 2013, collecting their blood for analysis and then tracking them until they gave birth. While initial versions of the test looked at a total of nine peptide or protein markers, the final panel consists of just two markers, the proteins insulin-like growth factors binding protein 4 (IBP4) and sex-hormone binding globulin (SHBG).

This winnowing down of the panel to two analytes is particularly interesting giving Sera's decision to launch the test commercially on a mass spec platform. While mass spec offers a number of potential benefits as a platform for clinical proteomics, one of the major advantages is its multiplexing ability and, in particular, the fact that costs remain relatively constant even as you add analytes to a panel. This contrasts with immunoassay-based tests where cost rises as the size of the panel expands due to the need for additional antibodies to each additional target analyte.

Given the small size of the PreTRM panel, mass spec presents less of an advantage in this respect. Nonetheless, Critchfield said, the technology remained attractive to Sera even after it became clear that the final test would feature fewer analytes than did earlier versions.

The company arrived at the two-protein panel "through a series of iterative discoveries that took place over a couple of years," he said.

"We saw that it was heading towards this," he added. However, "it made no difference to us in terms of the format of the test that we offered initially. And so we always planned on having a mass spec version of the test initially."

Multiplexing aside, "one of the most immediate advantages is that you can go directly from discovery and development straight into commercialization with no translational difference in performance," Critchfield said. "So it actually allows you to take it to market much sooner."

Additionally, Critchfield noted mass spec's potential for improved quantitative precision, a commonly cited benefit among proponents of the technology. While immunoassays can suffer from issues of background and interference, a mass spec assay should, in theory, measure only the exact analyte being targeted (though issues like the reproducibility of trypsin digestion make mass spec-based quantitation tricky, as well.)

The test's launch marks a significant step for clinical mass spec as the company becomes the second to bring a multiplexed, MRM mass spec-based proteomic test to market, following in the footsteps of Integrated Diagnostics, which launched its Xpresys Lung cancer test in 2013.

Given the small size of the test panel, though, Critchfield said Sera plans to explore other formats, including possibly immunoassays. In particular, the Bill and Melinda Gates Foundation, which is an investor in Sera, is interested in exploring the test's potential in underserved parts of the world, Critchfield said. An immunoassay-based test would be a likelier format for such settings than mass spec given the expense and infrastructure typically involved with the latter platform.

An immunoassay panel could also prove easier to take through the US Food and Drug Administration and other regulatory agencies were Sera to decide to offer the test in an in vitro diagnostic kit format in the future. Critchfield said that this was a possibility down the road.

"Our strategy has always been to offer the test as a mass spec-based test initially in a CLIA laboratory," he said. "If we are able to translate the technology to another form where there could be kits built then … we would need to go through proper regulatory authorities, and that would be the strategy in the future. But we are not there yet."

In addition to the validation data, Sera presented two other studies at this week's meeting. One detailed an effort using biomarker data to look at the mechanism underlying preterm birth. In that study, the researchers used multiple-reaction monitoring mass spec to measure 148 proteins across multiple pathways, exploring their potential roles in preterm birth.

They identified 25 proteins showing significant expression differences in preterm versus term subjects, finding 12 were associated with acute phase response and immune function, seven were linked to growth factor pathways, and three were involved in extracellular matrix remodeling and cell migration.

The second study described the initial discovery and verification of the PreTRM panel. For this work the researchers analyzed 148 candidate markers from the serum of 312 subjects consisting of 104 preterm cases (birth prior to 37 weeks gestation) and 208 controls drawn during gestational age of 17 to 25 weeks.

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