A New Use of an Existing Migraine Med Could Stop Your Headaches Before They Start
Like many chronic conditions, migraines disproportionately affects women. In fact, migraines are three times more common in women than in men and the fourth leading cause of disability in women, according to a 2020 study published in the journal Women’s Midlife Health. Not only that, but the frequency of headaches and the burden of migraine frequently worsens during midlife, Dr. Jelena Pavlovic, a neurologist and associate professor at Montefiore Einstein—and author of the 2020 study—notes.
Given the impact of migraines on midlife women, any advancements in treatment are a major step forward in quality of life.
Recently, an existing drug called ubrogepant went through phase 3 clinical trials demonstrating that it can also be used to stop migraine headaches before they even start and could help with pre-headache symptoms, according to an article published in the journal Nature Medicine.
Here’s what to know about the medication and what it could mean for midlife women.
What Is Ubrogepant?
Ubrogepant is an oral medication currently used to treat migraine symptoms, particularly severe, throbbing headaches that can be accompanied by nausea and sensitivity to sound or light. According to Pavlovic, it has been shown to effectively and safely treat migraines in women.
“It belongs to a novel drug class called gepants, which target a migraine-specific mechanism,” she explains. “This differentiates this group of medications—including ubrogepant, rimegepant and zavegepant—from commonly used over-the-counter medications, which do not act in migraine-specific ways.”
The FDA approved ubrogepant under the name Ubrelvy in December 2019. The medication is taken on an as-needed basis—rather than a daily preventive regimen—and is approved for the acute treatment of migraines with or without aura in adults, but it isn’t indicated for migraine prevention, says Dr. Danielle Wilhour, a neurologist and headache specialist at UCHealth.
“[Ubrogepant] has not historically been used to prevent migraines but rather to treat migraines once they begin, offering an alternative to triptans without the vasoconstrictive risks that can limit triptan use in patients with cardiovascular conditions,” says Dr. Deena Kuruvil, a neurologist and the medical director of the Brain Health Institute.
Importantly, ubrogepant differs from other acute migraine treatments like triptans and NSAIDs in that it doesn’t cause vasoconstriction—the narrowing of blood vessels. In addition, it is generally better tolerated and is safer in patients with cardiovascular risk factors, Wilhour explains. One thing to note is that ubrogepant can be expensive, with an out-of-pocket cost of more than $1,000 for 10 tablets, she says.
What Were the Results of the Phase 3 Trials?
Currently, ubrogepant only has FDA approval for the acute treatment of migraine. However, its manufacturer, AbbVie, is investing heavily in clinical trials to demonstrate broader effectiveness, says Dr. Hamid Djalilian, the director of otology and neurotology and a professor of otolaryngology, neurosurgery and biomedical engineering at the University of California, Irvine, chief medical advisor at NeuroMed Tinnitus Clinic, and past president of the Migraine in Otolaryngology Society.
“While ubrogepant is already on the market for acute migraine treatment, a new FDA indication—in this case, for intermittent preventive use—requires a separate application and approval pathway,” Kuruvil explains.
The aim of PRODROME, the name of the recent phase 3 trial, was to demonstrate that ubrogepant can also stop headaches before they start.
“Recent research has focused on whether the drug can be used even earlier, during the prodrome, the initial phase when patients sense a migraine is coming but before the pain starts,” Djalilian says.
During this phase, people with migraines often develop symptoms that are characteristic and recognizable, like dizziness, fatigue, difficulty focusing, sensitivity to light (photophobia) and sound (phonophobia), neck pain and stiffness before the onset of actual head pain, Pavlovic explains.
“In the PRODROME trial, ubrogepant not only reduced the chances of the headache developing, but also relieved non-pain symptoms like photophobia, neck pain, phonophobia, dizziness, fatigue and difficulty concentrating,” Djalilian says. “Some effects were observed as early as one hour after taking the medication.”
So, what’s next for ubrogepant?
“If these findings continue to hold up, they could strengthen AbbVie’s push to expand FDA approval, shifting ubrogepant’s role from only treating migraine pain to cutting off the attack before it starts, moving care from reactive to preemptive,” Djalilian explains.
AbbVie will likely submit a Supplemental New Drug Application (sNDA) to the FDA, Kuruvil says. The FDA will then evaluate whether the risk-benefit profile justifies ubrogepant’s expanded use, she adds.
What Does This Mean for Midlife Women?
Midlife women are hit harder by migraines, especially as the early stages of menopausal transition begin, Djalilian says.
“The uptick in migraine[s] during midlife is driven by fluctuations in estrogen and alterations in hormonal pathways that happen during perimenopause,” Pavlovic explains. “Women undergoing perimenopause often face unique challenges requiring specialized management of migraine[s].”
Not only are migraine attacks worse for midlife women, but they often become more frequent, longer-lasting and less responsive to treatment, Pavlovic notes. That said, after menopause, when estrogen levels stabilize at a lower level, migraine prevalence and frequency typically decrease, Wilhour says.
For midlife women whose migraines are hormonally driven, gepant drugs like ubrogepant may be helpful, but the jury is still out, Djalilian says. “Hormone-mediated migraine is distinct physiologically from other migraine classes,” he explains. “It’s fair to say that the use of gepants for menstrual or perimenopausal-related migraine is understudied, and recently, some migraine researchers have been fairly critical of their use before having more research to support it.”
If ubrogepant gains approval for preventive use, it could be a game-changer for midlife women who experience predictable migraine triggers, like menstrual cycles (in perimenopausal women), hormonal therapy transitions, travel, sleep disruption or high-stress periods, Kuruvil says.
“Unlike daily oral preventives or monthly injections, intermittent prevention with ubrogepant would allow these women to target vulnerable windows with flexible dosing, fewer side effects and no cardiovascular contraindications,” she says. “That flexibility is particularly valuable for patients who don’t want or tolerate daily preventive medications.”
It would also be part of a larger paradigm shift in migraine care—away from one-size-fits-all daily regimens, toward precision-based, patient-driven treatment models, Kuruvil says, adding that the development of gepants like ubrogepant opens the door to personalized, well-tolerated preventive strategies.
“Having an effective, safe and well-tolerated treatment option before the actual headache pain of [a] migraine starts can provide significant relief to many women, not only in terms of symptom treatment, but also by improving the quality of life by decreasing the overall time spent with migraine[s],” Pavlovic says.
