Daisy Farrar loves swimming, watching Bluey, and collecting stuffed animals. Some days the four-year-old pretends to be a princess, wearing sparkly shoes and a pink dress with a tulle skirt while she roams her family’s wooded three-acre property in rural North Carolina. Other days she’s more into robots, playing with Optimus Prime figurines with her dad. “To me, she is perfect,” says her mom, Brandi Starling Farrar. It’s a sentiment any loving parent might express—but in Daisy’s case, the fact that she is a happy, healthy kid is nothing short of incredible.
Daisy made history before she was born—she was the first person to receive nipocalimab, an experimental drug that helped her survive a rare fetal disease. Daisy and Brandi were among thirteen pairs of expectant mothers and babies who took part in a clinical trial led by Dr. Kenneth J. Moise Jr., a professor at Dell Medical School, in Austin. All were afflicted with hemolytic disease of the fetus and newborn, or HDFN, a rare, life-threatening condition that occurs in only about 8 in 100,000 pregnancies.
Most of the women in the trial, including Brandi, had previously had a miscarriage or lost a newborn to the condition. But thanks to the new drug, given via weekly intravenous infusions, all but one of the mothers gave birth to a healthy child. “The results were dramatic,” says Moise, a maternal-fetal medicine specialist and lead author of the study, which appeared in August in The New England Journal of Medicine. “That was very different from their previous pregnancies, where about a third of the women took a baby home.”
HDFN causes a mother’s immune system to attack her child. This happens when the two have different blood types, leading the mother’s body to react as though the fetus represents a threat. Testing for blood type incompatibility is standard in prenatal care, and a medication called RhoGAM has made the disease much less common than it once was—at least in developed nations, including the United States, where the injection is widely available. But the shot is effective only against the most common type of the ailment. Rarer variants, including what’s called Kell incompatibility, the kind Brandi and Daisy had, aren’t preventable. HDFN also persists among women without access to prenatal care, often because of a lack of insurance coverage. Texas has, by far, the largest uninsured population in the U.S.
A mother’s health isn’t affected by HDFN, but her fetus may become ill with anemia, extensive swelling, and heart failure, among other serious problems. The only treatment available is an ultrasound-guided blood transfusion, a high-risk fetal surgery in which a doctor guides a tiny needle into the fetus’s umbilical cord. “We may have to repeat the surgery four or five times during the pregnancy, and there are complications—losses for babies and infections in the mom,” Moise says. (With the new experimental drug, more than half of the thirteen women in the trial never needed a transfusion.) In cases of HDFN diagnosed before twenty weeks of gestation, even with the best care, the risk of death is about 20 percent. “So the idea for this drug was to not have to go through any of that.”
Brandi Farrar lost a daughter, Michelle, in 2016. Eight years later, the experience remains difficult for her to discuss. Brandi was twenty weeks along when routine prenatal testing and ultrasounds showed that her baby was sick, but HDFN is so rare that it took three more weeks to get a diagnosis. “They didn’t know what was wrong,” Farrar says. “I got passed around from hospital to hospital with no answers.” She was finally referred to a maternal-fetal medicine specialist who attempted an intrauterine blood transfusion. Michelle didn’t survive the procedure.
“I just remember they said her heart rate was fading, and they were going to stop,” recalls Brandi, who then spent two days in labor before giving birth to her stillborn child. Next came long, grueling months of learning to live with grief. During that dark time, she says, “I just did everything I could to get myself out of bed.”
When she learned she was pregnant again, three years later, she sank into another depression, worried she would have to bury another child. Because HDFN usually becomes more severe with each pregnancy, the odds seemed even longer than they’d been for Michelle. Brandi’s doctor in North Carolina put her in touch with Moise, who called to ask if she would consider joining the trial. When Brandi, who was working as a cashier at the time, told the researchers that she and her husband, Michael, couldn’t afford to travel to Texas for treatment, Moise and his team appealed to the trial’s sponsor, Johnson & Johnson. The company agreed to cover Brandi’s airfare and accommodation costs.
In her third trimester, when it became too risky for her to fly between North Carolina and Houston, Brandi moved into an apartment within walking distance of Children’s Memorial Hermann Hospital, where she received the infusions. “I was truly blessed with the whole experience,” she says. “Being in the trial changed my life.” To pass the time between appointments, Brandi and her husband explored Houston’s museums (the dinosaurs at the Houston Museum of Natural Science were Michael’s favorite—“He became a child again,” Brandi laughs) and restaurants. “My absolute favorite was the Mr. Miyagi taco at Torchy’s,” she says. “I ate that taco every chance I could.”
Because Daisy was born via a scheduled C-section, Brandi could choose her daughter’s birth date. She picked November 13, one day before Michelle’s birthday, November 14. Daisy arrived free of any complications from HDFN other than jaundice (which affects 50 to 60 percent of all full-term newborns). After a few days in an incubator under a blue light, she went home healthy.
Nipocalimab is now undergoing a phase-three clinical trial, which will include 120 patients. Moise is cautiously optimistic that the drug could receive FDA approval within about five years after those results are published. Saul Snowise, medical director of the Midwest Fetal Care Center, in Minneapolis, who was not involved with the study, calls the development of nipocalimab “a huge shift in the playing field toward better outcomes” for patients with HDFN. “We’re all very pleased to see the potential of the drug,” he says.
This research represents a win not just for Moise and his patients, but for maternal-fetal medicine as a whole. A perceived lack of profitability discourages pharmaceutical companies from backing such studies, according to Snowise. “Fetal intervention is such a small field, and unfortunately a lot of the companies are motivated by return on investment, not by patient outcomes,” he says. “So it’s very hard to publish good data like this.”
Moise notes that almost all medications prescribed during pregnancy, even for common conditions, are given off-label, meaning they’re not FDA-approved for pregnant patients. That’s largely because the vast majority of clinical trials don’t include pregnant women, ostensibly to avoid any potential risk to the fetus. This problem was in the spotlight during the COVID-19 pandemic, after all the major vaccine manufacturers excluded pregnant patients from trials.
Studies focused on conditions affecting fetuses are even rarer, “because now you’re giving something to the mother to benefit the unborn, and that’s a whole different cup of tea when it comes to ethics,” Moise says. “To my knowledge, this may be the first clinical trial to be approved through the FDA where the mom’s healthy, but we’re giving her a medication with some risk to her, but to help her baby.” Brandi and the other women in the trial experienced virtually no side effects.
Nipocalimab also holds promise as a potential treatment for other autoimmune conditions, such as lupus, myasthenia gravis, and rheumatoid arthritis. That might explain why Johnson & Johnson, the clinical trial’s sponsor, agreed to fund the research. “The moneymakers are going to be adult diseases in large populations,” Moise says. “I think J&J saw the possibilities of a big return on investment.” Snowise says his colleagues in Minneapolis are already considering other possible applications for the drug, such as for a cardiac condition called congenital heart block.
Moise has dedicated his career to eradicating HDFN, earning a reputation that brings patients from thousands of miles away to see him. (Snowise, who was mentored by Moise earlier in his career, calls him “the godfather of transfusion medicine.”) When we spoke, Moise had just stepped out of the operating room at Austin’s Dell Seton Medical Center after treating a patient who flies from Chicago to Texas every three weeks for transfusions. Another patient came to Austin from Nairobi to see him.
“I still get humbled by how difficult these procedures can be,” he says. “My patient who flies from Chicago—I mean, that just upends her life. If we can get this medication approved, if patients could be treated locally without the inherent risks of surgery—well, I tell people that’s my swan song. If we get this approved, I’m retiring, I’m done.”
