Empaveli safely used in pregnancy, despite PNH complications
Mother had a poor previous response to Soliris treatment
![A woman cradles a swaddled infant in her arms.](https://pnhnews.com/wp-content/uploads/2024/05/parent-and-child.png)
Using Empaveli (pegcetacoplan) during a new pregnancy led to a healthy outcome for a mother and her baby boy, even though complications of paroxysmal nocturnal hemoglobinuria (PNH) arose.
The mother, who previously had two miscarriages and a poor response to Soliris (eculizumab), recovered from an episode of breakthrough hemolysis, when symptoms of PNH returned despite treatment, prompting an emergency delivery. Her son, who was born prematurely but healthy, has developed normally, researchers said in a report.
“This report provides an example of an effective [Empaveli] treatment regimen during and after a successful pregnancy, and can be used to guide subsequent research and real-world treatment decisions,” the researchers wrote in “A case report of pegcetacoplan use for a pregnant woman with paroxysmal nocturnal hemoglobinuria,” which was published in Research and Practice in Thrombosis and Haemostasis.
PNH occurs when the complement system, a cascade of proteins that forms part of the immune system, mistakenly identifies blood cells as a threat, leading them to be targeted for destruction, a process called hemolysis. The ensuing deficiency in blood cells, particularly red blood cells, compromises their essential functions, including the adequate delivery of oxygen to tissues. This disruption in oxygen supply can result in various clinical manifestations associated with PNH, such as anemia, fatigue, and shortness of breath.
During pregnancy, PNH may increase the risk of complications such as miscarriage and preterm birth. Growing evidence suggests Soliris, an antibody-based treatment that inhibits a complement protein called C5, may improve a pregnancy’s outcome.
A first use of Empaveli in pregnancy
Here, the researchers describe what they claim is “the first case study” on using Empaveli in a pregnant woman with PNH who didn’t respond well to Soliris. Unlike Soliris, Empaveli inhibits C3, which is upstream of C5 in the cascade of complement proteins. Both are approved to treat PNH.
The 33-year-old woman started Soliris shortly after her PHN diagnosis. She didn’t respond well to treatment, however, and required frequent red blood cell transfusions due to recurrent episodes of breakthrough hemolysis.
Despite an increase in dosing, the woman had two miscarriages, one at 12 weeks and another at 24 weeks gestation. She was switched to Empaveli, given as an injection under the skin, or subcutaneously, twice weekly. “She adhered very well to this treatment,” the researchers wrote.
Her hemoglobin, the protein that carries oxygen in red blood cells, increased from 8.1 grams per deciliter (g/dL) with Soliris to a normal 12.6 g/dL within two weeks of the switch. About four months after starting Empaveli, she became pregnant.
“We discussed with our patient that use of [Empaveli] during pregnancy had the potential for harm because [Empaveli] had not been tested during pregnancy and had the potential to cross the placenta,” the researchers wrote. “She understood these risks.”
Despite the potential for harm, the woman decided to continue on the same dose, which she received with enoxaparin starting her second trimester to prevent blood clots. Her hemoglobin remained stable during this period.
At 30 weeks of gestation, the woman had breakthrough hemolysis and abruptio placentae, which occurs when the placenta separates from the wall of the womb before the baby is born, prompting an emergency C-section.
She delivered a healthy baby boy and received intensive treatment for hemolysis with once-daily dosing of Empaveli for three days. To better control hemolysis, she also received two doses of Soliris given within a three-day interval. Hemolysis resolved within a week.
“Our patient responded well to [Empaveli] treatment before her pregnancy and during the first and second trimesters. Although she developed complications at gestational week 30, her premature infant was delivered safely and the breakthrough hemolysis she experienced was quickly reversed,” the researchers said.
The woman remained on maintenance treatment with Empaveli after being discharged from the hospital. Her hemoglobin levels were within normal range and she reported no blood clots. Empaveli wasn’t measured in the placenta or breast milk and the woman didn’t breastfeed her baby.