The drug that reduces symptoms that precede migraines and opens a new avenue for treatment

A new Phase 3 clinical trial, published this week in the journal Nature Medicine , has shown that the drug ubrogepant can not only relieve migraine pain, but also significantly reduce the symptoms that herald its arrival , such as light sensitivity, dizziness, and difficulty concentrating. This is the first time that a treatment has shown efficacy in the prodromal phase of migraine , which could represent a radical shift in the clinical approach to this condition that affects more than a billion people worldwide.

Until now, most treatments have focused on combating migraines once they have already begun . However, many patients are able to predict the onset of an episode several hours in advance, experiencing a series of premonitory symptoms such as fatigue, neck stiffness, nausea, or hypersensitivity to sensory stimuli. According to neurologist Dagny Holle-Lee , director of the West German Headache Center, "This study is the first to investigate whether migraines can be effectively interrupted in their prodromal phase," she told the Science Media Centre (SMC) .

The trial, led by neurologist Peter Goadsby , included 438 people aged 18 to 75 with a confirmed history of migraines. Participants took either 100 mg of ubrogepant or a placebo when they began to notice the first symptoms leading up to an attack, at which point they were convinced the pain would arrive within one to six hours. They then received the opposite treatment during another prodromal episode, in a double-blind, crossover design.

The results were overwhelming: within one hour of taking ubrogepant , patients reported improved concentration; within two hours , they reported less sensitivity to light; and within three hours , they reported a decrease in neck pain and fatigue. Furthermore, symptoms such as dizziness and sensitivity to sound also decreased over the following 24 hours , to a greater extent than with placebo.

A functional improvement for patients

Dr. Charly Gaul , director of the Frankfurt Headache Center, told SMC that "prodromal symptoms have a considerable impact on migraine patients." He believes that light sensitivity —frequently cited as the most bothersome symptom—and others such as concentration problems or neck pain directly affect daily performance and the professional environment .

According to the exploratory analysis of the PRODROME study, on which this new publication is based, 46% of patients treated with ubrogepant in the prodromal phase did not develop into moderate or severe headaches in the following 24 hours, compared to 29% in the placebo group. As for pre-existing symptoms, the drug was able to eliminate them in significantly higher percentages: for example, three hours after taking the drug , fatigue had disappeared in 27.3% of cases treated with ubrogepant, compared to 16.8% in the control group.

The beginning of a new strategy?

Experts agree that the data, although promising, need to be confirmed in trials specifically designed to measure ubrogepant's efficacy in the prodromal phase. "Exploratory analyses cannot replace prospective clinical trials," Gaul clarifies, although he emphasizes that the drug's potential "represents a significant improvement for migraine patients," especially because current treatments—such as triptans —are only indicated once the pain has begun.

Ubrogepant belongs to a new class of medications called gepants , which block the CGRP receptor , which is involved in pain transmission. Unlike triptans, these medications are better tolerated and do not pose a risk of medication overuse headaches, reinforcing their usefulness in the early stages of an attack.

At the moment, ubrogepant is not yet approved in Europe , although other gepants with similar characteristics, such as rimegepant or atogepant , are expected to arrive. Holle-Lee tells SMC that “a possible EMA approval would be positive, as the early use of ubrogepant would be even more attractive.”

Still no data on the aura

A key clarification of the study is that ubrogepant's efficacy has not been evaluated in the aura phase , the other early stage of migraine characterized by visual or neurological disturbances. Both Gaul and Holle-Lee emphasize the need to clearly distinguish the prodromal phase from the aura phase , as the underlying biological mechanisms are distinct.

In conclusion, experts believe that ubrogepant opens up a new avenue for therapeutic intervention. "Any additional therapeutic option improves the situation for those affected," Holle-Lee summarizes.