Cedars-Sinai Investigator Studies Monoclonal Antibody Eculizumab in Pregnant Women With COVID-19, Preeclampsia
Feb 25, 2021 Cedars-Sinai Staff
Pregnant women with severe illness present a particular challenge to providers. Rarely are these patients included in clinical research studies due to concern for both mother and child, and very few new drugs are approved for use.
Richard M. Burwick, MD, MPH, assistant professor, Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, is working to change that.
“If we don’t figure out a way to include pregnant women in more clinical trials and investigate the safety of new therapies, there’s going to be a huge gap in care. Medical innovations are happening rapidly, and pregnant women are getting left behind.”
Seeking a safe COVID-19 treatment for pregnant women
Even when clinical trials involving pregnant women are approved, they are often limited by funding constraints and the ethical considerations of working with this patient population.
“You have to be cautious when investigating new treatments in pregnant women,” Burwick says. “But I believe there is strong rationale to include them in clinical trials, especially when faced with a disease such as COVID-19, where there is risk of serious harm to both mother and fetus.”
A severe case of COVID-19 can mean long-term tissue damage or undesirable outcomes like premature delivery or, in very severe cases, maternal death.
“The literature says the risk of premature delivery for pregnant women with severe COVID-19 illness is 30-40%. This is not because COVID-19 causes early labor, but because the patient’s COVID-19 illness is worsening and providers have few treatment options besides premature delivery.”
With little research available, physicians resort to prescribing drugs off-label or that have been approved for compassionate use. Sometimes, they choose not to prescribe drugs at all due to a lack of safe options or fear of adverse effects to the fetus.
“Excluding expectant mothers from clinical trials could potentially lead to increased harm, because providers and patients are hesitant about new treatments that lack safety and efficacy data in pregnancy,” says Burwick.
Burwick believes there is a better way, noting that prescribing drug therapies through clinical trials—with a protocol approved by the Food and Drug Administration and the Cedars-Sinai Institutional Review Board (IRB)—is safer than prescribing them off-label or via compassionate use approvals. Clinical trials also allow superior data collection compared to retrospective investigations.
Targeting the immune response to defeat COVID-19
Since the beginning of the pandemic, physicians have searched for safe, effective treatment protocols for pregnant women with COVID-19. One drug—eculizumab—shows promise. Eculizumab targets the complement system and works by lowering immune-mediated inflammation and tissue damage, so the body can heal from illness and stop attacking its own healthy cells.
“The complement system is your innate immune system,” says Burwick. “In a disease like COVID-19, you have no antibodies, and you rely on your innate immune system for immediate defense against foreign pathogens.”
In some cases of severe illness, Burwick says, the body’s innate immune system works too well.
“When a foreign pathogen is introduced—COVID-19 in this case—your complement system tags the virus as a foreign body and triggers your immune system to attack. But when the virus has replicated in large volume and spread deep into healthy tissue, your immune system can mistakenly begin to attack and damage healthy cells.”
Drugs like eculizumab block the membrane attack complex, the final complex formed in the complement system cascade, and prevent the body from causing additional injury to itself.
Eculizumab has been FDA-approved for more than 10 years to treat two rare blood disorders, and has yielded good safety data when used in pregnant and lactating women. It’s unique design limits transport across the placenta during pregnancy and it doesn’t get into breast milk, unlike many other monoclonal antibody therapies.
Encouraged by similar trials using complement blockades to treat COVID-19 patients, Burwick launched a small study that uses eculizumab to treat pregnant and lactating women with severe or critical forms of the illness. Initial data is encouraging.
From COVID-19 to preeclampsia and beyond
Building on this promising work, Burwick will soon begin investigating the efficacy of treating preeclampsia using eculizumab, targeting the same part of the complement system.
“There are similar issues with the complement pathway, except this time the foreign body is the placenta rather than a virus,” says Burwick. “In normal pregnancy, the complement system is key to keeping the fetus healthy, but it’s important that it does not attack the placenta as it does with foreign pathogens.”
Historically, there has been some hesitation to mount clinical studies for pregnancy-related conditions because of the inability to test new therapies and treatments for safety in a nonpregnant population first.
But some conditions, like preeclampsia, only exist in pregnant women.
“If we don’t figure out a way to include pregnant women in more clinical trials and investigate the safety of new therapies, there’s going to be a huge gap in care,” Burwick says. “Medical innovations are happening rapidly, and pregnant women are getting left behind.”