The Food and Drug Administration recent approval of Aimovig, a new preventative treatment against migraines, came as good news for the millions in the United States who suffer from the debilitating headaches. It’s the first approval for a new group of drugs that block a particular molecule that is elevated during migraine, designed to reduce the frequency and severity of migraine attacks.
Most drugs available today reduce migraine symptoms, but Aimovig aims to stop them from happening as frequently. In three clinical studies, patients taking the drug had one or two fewer headache days per month than those taking a placebo. The drug is delivered as a once-monthly injection, and has a sticker price of $6,900 a year.
Matthew Robbins, associate professor of neurology at Albert Einstein College of Medicine, told The Daily Beast that the approval is exciting, and represents the first step forward for a new, promising class of migraine treatments. However, he said, for a subset of migraine sufferers, there’s a lingering safety concern.
Migraines disproportionately affect women (they strike 18 percent of women, compared to six percent of men), and specifically, women of an age where they might become pregnant. But despite the drug’s approval and stamp of safety, the research process didn’t come to any conclusions on the safety during pregnancy, either for the mother or the fetus. That leaves doctors cautious to recommend the treatment for women who are or may become pregnant.
“This issue is going to come up for a big group of people who want to use the medication,” Robbins said. “There’s no safety data available on it.” The FDA’s label specifically says that there is no data on any risks associated with the drug’s use in pregnant women.
Aimovig isn’t unique, in this respect. Most drugs, due to ethical concerns, aren’t tested in pregnant women, and that means we don’t have many drugs that are specifically labeled as safe to use during pregnancy. Because of the demographics of those with migraines, Robbins said it’s particularly important to note that gap in this new drug.
“Right now, I would not recommend it for women of a childbearing age,” Elizabeth Loder, chief of the division of headache in the department of neurology at Brigham and Women’s Hospital, told The Daily Beast. “Women in that position should be warned about the unknown safety in pregnancy. I wouldn't withhold it, if they knew the risks, but I wouldn’t recommend getting pregnant while on treatment—however, we know that unintended pregnancies will occur.”
For many women, migraines actually subside during pregnancy, but for those still affected during that period, there isn’t a gold standard for treatment. “We try to reduce exposure to medication,” Loder said. Some medications commonly prescribed for migraines, like lisinopril and topamax, are clearly linked to negative outcomes, and are avoided entirely. In other medications, there is limited but non-conclusive information on safety during pregnancy—which some doctors are comfortable with, while others aren’t.
Based on its mechanism, Loder said that there’s reason to be cautious that Aimovig could potentially affect a pregnancy. The drug blocks the receptor for the calcitonin gene-related peptide, or CGRP, a protein that dilates blood vessels and that spikes during migraine. According to research in pregnant rats, the molecule is involved in pregnancy.
“The drug affects a substance widely distributed in the body, and plays a role in many bodily process,” Loder said. “Theoretically, we might worried about any pregnancy related process that requires vasodilation—though it’s completely speculative.” Aimovig also sticks around in the body for as long as month, unlike other treatments, which can clear the system in as little as a day.
Some preclinical studies also show that levels of CGRP go down during the development of pre-eclampsia, a pregnancy complication marked by dangerously high blood pressure. If Aimovig leads to dampened levels of CGRP, there could be concerns that it would increase risk of pre-eclampsia, Robbins said—though, he stressed, that’s entirely hypothetical at this point.
“There’s a greater unknown as this medicine is new,” he said. “And there are potentially more theoretical risks associated with this particular medicine.”
A study done in monkeys during the drug development process did not find any adverse effects from the drug on birth outcomes, but animal studies don’t always transfer to humans, Loder said. The drug probably would not have moved forward if there *was* evidence of a problem, but animal studies with positive results don't always transfer to humans, Loder said. “It’s nice, but it doesn’t completely reassure anyone.”
Novartis and Amgen, who developed the drug, will continue to gather information about Aimovig and pregnancy as patients begin to take it in what’s called a post-marketing study. As a condition of approval, the FDA asked them to build a registry of patients who do become pregnant while taking the drug, and track any potential negative safety outcomes that come up. “I’m pleased to see that they’re requiring that,” Loder said. Registries one of the best ways to learn about drug effects, she said — though they’re difficult, and take a lot of time. “It’s very hard to get healthcare professionals to report the pregnancies.”
Loder was involved with the pregnancy registry for another migraine medication in the late 1990s for a drug called sumatriptan, then marketed by GlaxoSmithKline under the brand name Treximet. The final results were published in 2014. It didn’t find a significant increase in adverse birth outcomes among the 626 women taking the medication while pregnant, but the results weren’t enough to conclusively say if it’s safe. The registry just wasn’t able to include enough cases to say for sure. The limited safety data, though, is enough to reassure some doctors who go on to prescribe the medication, Loder said.
With social media, Loder hopes that Novartis and Amgen will have more success publicizing the registry, and speeding that process along. Amgen is currently working with the FDA to develop the registry, and don’t have details about it available at this time, a spokesperson wrote in an email to The Daily Beast.
Other drugs that also target CGRP are in development at other pharmaceutical companies, and they’re likely to also be FDA approved soon. Robbins said that the same concerns around pregnancy would be similar, and he’d expect that the FDA would require continued monitoring of their effect on pregnancy, as well.
“I’m very enthusiastic about this class of medicine,” he said. “There are just a lot of unknowns.”