NEW YORK – Pregnancy health firm Mirvie said this week that it is close to the launch of the first RNA-based blood test to predict pregnant individuals' risk of developing preeclampsia, a hypertensive condition that can lead to preterm birth, after generating positive data from a study that analyzed more than 9,000 pregnancies.
Published on Tuesday in Nature Communications, the study provided a validation of the performance of Mirvie’s test to predict preeclampsia at 17.5 to 22 weeks gestational age, in patients without clinical risk factors.
It also explored other molecular patterns that could be useful in managing the larger family of hypertensive disorders of pregnancy, including distinguishing between severe and mild cases and identifying pregnancies at risk of spontaneous preterm birth.
Founded in 2018, the San Francisco-based company published a pair of baseline studies in 2022, including a paper in the American Journal of Obstetrics and Gynecology, demonstrating that cell-free RNA profiles could help predict spontaneous preterm birth, and another, in Nature, demonstrating that cfRNA could specifically predict preeclampsia.
Thomas McElrath, Mirvie's VP of clinical development, said in an interview that most of the interim time has been devoted to completing this much larger study in anticipation of a nationwide launch of the test, now branded as Encompass. The assay is already available online as part of an early access program, but the firm has not yet begun to market the test broadly.
"The study rolled out just at the end of COVID, so that made it a little more challenging, but there were a lot of patients enrolled around the country in a nationally representative fashion," he said. "We're doing something a little bit revolutionary which is really … trying to change how prenatal care is executed."
Although there are known interventions for pregnancies at a high risk of preeclampsia, namely daily aspirin, use of these strategies is limited, McElrath said, due to the limitations of current guidelines for assessing risk.
"By the time a patient is symptomatic, it's a race against the clock to try to get the baby to term and not risk the mother's health," Kara Rood, one of the principal investigators of the study and a clinical associate professor at Ohio State University's Wexner Medical Center, said in a statement.
"Current guidelines are not helping us identify which patients are truly at high risk and we need better tools," she added.
In the study, investigators calculated that Mirvie's test identified 91 percent of pregnancies that went on to develop preterm preeclampsia in women 35 and older who had no clinical high-risk factors. Less than 1 percent of individuals with a low-risk test result developed preterm preeclampsia.
McElrath said that the more comprehensive validation results are a first step to supporting adoption and hopefully future insurance reimbursement for the test, which is currently listed on its website at a price of $1,850.
"You're not going to get physicians, and then by extension, payors, to come on board without significantly demonstrative data, and I think this really helps move things along from where that first paper left us," McElrath said.
Encompass is currently provided as a patient-order test under the firm's early-access program. Patients can order a test kit and schedule an at-home blood draw by a mobile phlebotomy service. Results are returned within 14 days and can be simultaneously sent to the patient's physician.
In the past, direct-to-consumer medical tests have come under scrutiny by the FDA, but McElrath said that the company does not believe it is at risk, as direct patient access to test results across healthcare has evolved in recent years.
To a certain extent, the company's strategy follows what was seen early in the evolution of noninvasive prenatal tests for Down syndrome and other fetal aneuploidy disorders.
With NIPT, a new molecular technology was being put forward in the context of existing modern diagnostic tools, namely amniocentesis. But for preeclampsia, there has been virtually no technological development in diagnostic or prognostic testing for arguably a century, McElrath argued.
"I think you could probably get a doctor from the 1920s and say, hey, here's my patient with preeclampsia, and they would probably give you a pretty accurate summary of what the disease is and how to treat it. We haven't really had any second and third trimester innovation in the field, and it is in the second and third trimester that most of the neonatal morbidity and most of the morbidity to mothers really occurs," he said.
A central goal for Mirvie will be to prove to the field that its test is not only valid but also useful — that earlier and more accurate detection of preeclampsia risk can lead to interventions that improve maternal and fetal outcomes.
"We've developed the test and now we're getting into what to do with that information," McElrath said.
With data in hand from the firm's newly published study, the company is also working on additional applications, including expanding the Encompass test to a broader age group, and to patients who do have existing clinical risk factors. Investigators are also digging into whether the company's RNA platform can help improve care for other pregnancy complications, such as fetal growth restriction, and spontaneous preterm birth, which McElrath said is "probably the single largest complication of pregnancy among what are called the great diseases of pregnancy."
"Hopefully where we see this in seven years or so is that a patient can have a blood test done and it will screen that patient for [multiple risks] so their care plan can be very individualized," he added.
"Maybe another patient will come along and is at risk for nothing," McElrath added. "That patient could then have a care experience that might be more tailored to their personal preferences. Maybe they want to see a midwife; maybe they don't want to be seen once every two weeks."
On the flip side, if a patient had a high-risk result for spontaneous preterm birth, her physician could follow her cervical length more closely.
With its upcoming broader launch of Encompass, Mirvie has developed a set of support materials for patients and physicians outlining prevention strategies for patients who receive a high-risk test result, hoping to kickstart the development of an evidence base for clinical utility.
"There are a lot of things that can be done, but we've settled on some of the things that are most proven, and that essentially relies on administration of aspirin." McElrath said.
The company plans to study a higher dose than is currently recommended, based on recent research suggesting that it may be more effective, and will follow patients' real-world outcomes.
McElrath said that the company also believes there is a great opportunity for the research community in the larger data it was able to collect from the 9,000 pregnancies it analyzed samples from.
"I think the biggest piece is that we're demonstrating that this isn't a monolithic disease. I think the technical term is that it's a convergent phenotype. You've got multiple different pathways that lead into a more stereotypic clinical presentation," he said.
Some of the early insights from the study include evidence for molecular and immune features separating subgroups of patients such that that the biology of earlier presenting and more morbid cases of preeclampsia is different than that of later-presenting hypertension.
"Interestingly, we couldn't actually distinguish between preeclampsia and the condition of gestational hypertension because the markers overlap," McElrath said.
It's something physicians have suspected for some time — that what the field calls gestational hypertension, which does not involve the same level of clinical concern as preeclampsia, is probably something that is prone to evolve into preeclampsia.
"It suggests that maybe patients with preeclampsia late in pregnancy really don't need to be treated with the same medical intensity and acuity as the patients who have preterm preeclampsia. Maybe they can be managed expectantly or managed so that the [fetus] has an additional couple of weeks of gestation towards a better neonatal outcome," McElrath said.
"There has been the idea that maybe we're unnecessarily ending these pregnancies out of our concern that this is one monolithic disease, and this data begins to offer some of the epidemiologic and molecular substructure to look into that," he added.
Mirvie is also planning to explore the possibility of drug repurposing by investigating pharmacologic databases for genes that feature in its preeclampsia subtype data.