Zofran birth-defect lawsuit rejected by First Circuit

BOSTON (CN) — More than 400 families whose children suffered birth defects after their mothers were prescribed Zofran for morning sickness lost their lawsuit Monday against the drug’s manufacturer.

“Plaintiffs fail to explain why this is any evidence at all of a causal association between Zofran and birth defects,” U.S. Circuit Judge William Kayatta wrote for a three-judge panel of the First Circuit.

Pointing to three animal studies conducted in Japan 20 years ago that allegedly linked Zofran to a higher risk of fetal injuries, the families of babies born with cleft palates, skull deformities, heart defects and other problems wanted to hold GlaxoSmithKline liable for failure to warn.

Zofran (ondansetron) is approved by the U.S. Food and Drug Administration for nausea and vomiting caused by chemotherapy, radiation treatment and surgical recovery. The FDA has never approved it for morning sickness, but the drug is prescribed off-label for that purpose to as many as 25% of pregnant women, according to WebMD.

That’s in large part because there are few prescription medications approved for morning sickness; the most common other treatment is a combination of antihistamine and vitamin B6.

Drug companies aren’t allowed to promote their drugs for off-label uses, but GSK agreed to pay $3 billion in 2012 to resolve claims brought by the U.S. Department of Justice that it promoted several of its drugs, including Zofran, for uses that were unapproved.

GSK had mentioned the Japanese studies in an early FDA filing, but it downplayed them by claiming that they were conducted “specifically to satisfy Japanese regulatory requirements” and “provide no new significant safety information.”

GSK sold Zofran to Novartis in 2015. After parents started filing lawsuits against GSK, Novartis asked the FDA for a label change based on other birth-defect research, and GSK came forward with more details about the Japanese studies. But the FDA announced in early 2021 that it wouldn’t require a new warning label.

The families argued that GSK could have changed the warning label anyway, despite the FDA’s approval of its language, because the Japanese studies were newly acquired information.

But “the first problem for plaintiffs is that the risks they identify in the three Japanese studies — embryofetal death, major malformations including ventricular septal defects, and skeletal defects — were not found by the researchers in those studies to be attributable to Zofran,” Kayatta, an Obama appointee, wrote.

“Each of the three studies to which plaintiffs point concluded that there was no statistically significant relationship between Zofran and observed birth defects in animal subjects — that is, the studies concluded that incidences of birth defects were within the background range expected to occur naturally in the subjects.”

The families argued that the Japanese studies were different from other studies because they involved higher doses, but “the observed anomalies in the animal subjects were not dose-related,” Kayatta said.

Since the Japanese studies produced no new relevant information and since a company can’t change an FDA-approved label otherwise, Kayatta concluded that federal law preempted the families’ suits.

The families made an argument that the FDA wasn’t fully informed of any issues raised by the Japanese studies when it approved the label, but Kayatta said that wasn’t true because the plaintiffs themselves had informed the FDA about the studies.

The plaintiffs “beat the FDA over the head with these animal studies,” GSK’s lawyer, Lisa Blatt of Williams & Connolly in Washington, told the panel at oral argument.

Kayatta concluded that “the fully informed FDA in approving the label stating ‘not-X’ necessarily rejected plaintiffs' prominently presented case for stating ‘X.’ … When the FDA formally approves a label stating one thing with full and obvious notice of the directly contrary position, one can read the approval as rejecting the contrary position.”

Kayatta was joined on the Boston-based panel by U.S. Circuit Judge Jeffrey Howard, a George W. Bush appointee, and U.S. District Judge Lance Walker, a Trump appointee sitting by designation from the District of Maine.

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