Q&A: Novel biomarker test identifies 14-day risk for preeclampsia

Researchers said a blood test that assesses multiple biomarkers can rule out a pregnant person’s risk for developing preeclampsia in the next 14 days.

They presented data on the Preecludia (Progenity) test at the American College of Obstetrics and Gynecology Annual Clinical and Scientific Meeting.

The study population comprised of 376 participants (71% white) aged 18 to 45 years who presented with at least one sign or symptom associated with a risk for developing preeclampsia. Among the study population, 254 participants were never diagnosed with preeclampsia and 122 participants were diagnosed with preeclampsia during their current pregnancy.

The researchers gathered blood samples and categorized the participants as either having a reduced risk for preeclampsia within the next 14 days or being at risk for developing preeclampsia. They reported that the test performed with high sensitivity and had a high negative predictive value to rule out preeclampsia risk.

Healio Primary Care spoke with Matthew Cooper, PhD, DABT, MBA, the chief scientific officer of Progenity and first author of the study, to learn more about the test and when it will be widely available in the U.S.

Healio Primary Care: What prompted the development of the Preecludia test?

Cooper: A personal, near-death experience during the birth of my son. My wife had the classic signs and symptoms of preeclampsia, but our physician missed them and managed the pregnancy improperly as a result. It was only after they started emergency, lifesaving procedures that the doctor lamented, “I guess it was preeclampsia.” It was the first time I had ever heard the term and it stuck with me for obvious reasons. Years later, I encountered a project at Stanford, where I was an advisor, discovering biomarkers for preeclampsia. I leapt at the opportunity to tackle the condition. There’s been no advancement in the diagnosis and treatment of preeclamptic patients for over 100 years and I knew we were on to something. I spent hours upon hours interviewing OB-GYNs to understand the intricacies of the unmet clinical need. Currently, the diagnosis of preeclampsia is not based on a definitive, diagnostic test and the evaluation of suspected preeclampsia is cumbersome and relies on a multitude of nonspecific, surrogate maternal and fetal evaluations. Tools used today, such as BP readings and urine protein tests, are not very sensitive or specific. Lots of things increase BP; lots of things cause proteinuria. I thought it was time to bring the diagnosis of the syndrome into the age of molecular medicine by evaluating biomarkers tied to the underlying pathophysiology.

Preeclampsia presents in different ways for different people, and we know that overlooking mild signs may lead to a missed diagnosis and adverse outcomes, as happened with my wife. As a result, clinical diagnoses remain difficult and can result in early delivery, or worse. Preeclampsia is still the No. 2 cause of maternal and fetal mortality here in the U.S. It’s hard to believe that mothers and babies still die during pregnancy in the year 2021. Our test more accurately assesses the risk of developing preterm preeclampsia within 14 days, using biomarkers from multiple pathways involved in the underlying pathophysiology of preeclampsia. This could potentially avoid unnecessary interventions and premature delivery. I envision a future where no other family has to experience what mine did.

Healio Primary Care: How was it developed? What biomarkers does it evaluate?

Cooper: I was working with some colleagues at Stanford on applying a more modern, systems biology approach to the way we analyzed preeclampsia. We combined that with deep market insight from our interviews with OB-GYNs. Our conversations with these physicians led to several epiphanies. The first was that the biggest problem in the space was not about predicting preeclampsia, but about distinguishing symptomatic women at most risk from those at a reduced risk. The second was that giving doctors a high degree of confidence in a test result that’s negative for preeclampsia vs. a test result that’s positive will ultimately change the way they are treating these patients and potentially reduce overuse of interventions and resultant complications. This led us to develop Preecludia, a propriety lab test that has the potential to be the first-of-its-kind test in the United States to help health care providers evaluate patients who have signs and symptoms of possible preeclampsia. This laboratory-developed test is a novel multianalyte protein biomarker assay designed to examine markers from multiple pathophysiological pathways of preeclampsia to assess risk.

The test has undergone more than 6 years of studies covering thousands of patients, including the latest PRO-129 verification study. This verification study, recently presented at the 2021 ACOG annual meeting, examined blinded blood samples from pregnant women at 24 U.S. sites to determine the ability of Preecludia to assess risk of preeclampsia within 14 days of sample collection. The samples were representative of a diverse U.S. population. Preecludia test performance, based on 303 subjects, showed a 97% negative predictive value, with 87.8% sensitivity. That’s very promising! These data point to the value of the test in assisting physicians to rule out patients at risk for preeclampsia. By doing so, the test may provide reassurance to physicians and patients, and assist physicians in making better informed management and treatment decisions.

Multiple pathways are involved in the pathophysiology of preeclampsia. The Preecludia test combines eight biomarkers across pathways known to be involved in preeclampsia, such as anti-angiogenesis, trophoblast dysfunction, hypoxia and ischemia, inflammation and immune dysregulation, with gestational age in a sophisticated algorithm that reports a clear binary result for clinicians.

Healio Primary Care: How effective is the test?

Cooper: What gets me most excited about this product is it’s one product that can potentially save two lives — the mother’s and the baby’s. In women with suspected preeclampsia at 28 to 36 6/7 weeks, this study concludes that the Preecludia test has high negative predictive value and high sensitivity to rule out the risk of developing preeclampsia within 14 days, up to 37 weeks’ gestation. Test performance on 303 subjects showed 97% NPV and 87.8% sensitivity.

Healio Primary Care: When will it be widely available for use in the U.S.?

Cooper: The test is now in the final clinical validation testing phase, with a targeted launch expected in the second half of 2021. We’re anticipating it to be widely available in 2022.

Healio Primary Care: How can providers implement Preecludia in clinical practice?

Cooper: It’s designed to be a tool aiding in the assessment and management of preeclampsia. When launched, providers will be able to utilize the test with women in their third trimester (28 to 36 6/7 weeks) of pregnancy who are showing signs and symptoms of preeclampsia. It is run from a simple blood draw, and results are typically delivered within 24 to 48 hours. The test may provide reassurance to physicians and patients and assist physicians in making better informed management and treatment decisions, potentially reducing overuse of interventions and resultant complications.

Reference:

• Cooper M, et al. Performance of a novel multi-biomarker rule-out preeclampsia test: A prospective verification study. Presented at: American College of Obstetricians and Gynecologists Annual Clinical and Scientific Meeting; April 30-May 4, 2021 (virtual meeting).