Results published in The Lancet show Ubrelvy (ubrogepant) reduces the headache phase of a migraine attack when dosed during the prodrome of migraine

The Phase III study, PRODROME, showed that Ubrelvy given during the prodrome (i.e., 1-6 hours before the predicted onset of headache pain) significantly reduced the likelihood of development of moderate or severe headache and reduced functional disability compared to placebo within 24 hours post-dose.

The prodrome is the earliest of four phases of a migraine attack and consists of various symptoms, including sensitivity to light and/or sound, fatigue, and neck pain, that can be an early sign that the headache phase will follow. In people with migraine who experience a prodrome, symptoms can occur hours to days before the onset of headache. Treatment during the prodrome provides an opportunity to avoid the development or attenuate the severity of the headache phase of a migraine attack.

"Migraine impacts nearly 40 million Americans and is a highly debilitating disease that can cause people to miss work, and time with friends and family. For patients who are able to identify prodromal symptoms, the ability to treat a migraine attack before the headache phase creates an opportunity to stop migraine attacks before they become fully debilitating," said Dawn Carlson, vice president, neuroscience development, AbbVie. "These data published in The Lancet demonstrate the important role of Ubrelvy in treating migraine attacks early and reducing the overall burden of a migraine attack."

During the trial, patients with migraine who could identify prodromal symptoms that led to headache at least 75% of the time (N=518), were randomly assigned to double-blind crossover treatment. Study results demonstrated the following: i. Absence of moderate or severe intensity headache within 24 hours was achieved following 46% of qualifying prodrome events when treated with Ubrelvy vs. 29% of placebo-treated events (P<0.0001). ii. absence of moderate or severe intensity headache within 48 hours was achieved following 41% of qualifying prodrome events when treated with ubrelvy vs. 25% of placebo-treated events (p><0.0001). iii. more patients had normal function within the 24 hours after treatment of qualifying prodrome events with ubrelvy than after treatment with placebo [odds ratio (or) 1.66, 95% confidence interval (ci) 1.40–1.96; p><0.0001]. iv. absence of headache of any intensity within 24 hours was achieved following 24% of qualifying prodrome events when treated with ubrelvy vs. 14% of placebo-treated events (p><0.0001).

The safety population included 480 patients, and the efficacy analysis population included 477 patients. The most commonly reported prodrome symptoms in the study were sensitivity to light, fatigue, neck pain, sensitivity to sound and dizziness/lightheadedness. Ubrelvy was well-tolerated with no new safety signals observed when administered during the prodrome. The most common side effects are nausea (Ubrelvy: 5% vs. placebo: 3%), fatigue (Ubrelvy: 3% vs. placebo: 2%), dizziness (Ubrelvy: 2% vs. placebo: 3%), and somnolence (Ubrelvy: 2% vs. placebo: 1%).

"As a neurologist, I have many patients who can describe the premonitory, or prodrome, symptoms of their migraine attacks, and previously we have not had adequate data for treatment options during this earliest phase," said Peter J. Goadsby, M.D., Ph.D., FRS, neurologist and professor at King's College London. "These new data speak directly to a gap in migraine treatment and the option to use ubrogepant."

About the PRODROME study PRODROME (NCT04492020) was a Phase III multicenter, randomized, double-blind, placebo-controlled, crossover trial that enrolled adults who experienced 2-8 migraine attacks with moderate-to-severe headache per month. Eligible patients treated 2 "qualifying prodrome events" in a crossover fashion. A qualifying prodrome event was defined as a migraine attack with prodromal symptoms in which the patient was confident a headache would follow within 1-6 hours. The primary endpoint was absence of moderate/severe intensity headache within 24 hours post-dose. Secondary endpoints were absence of moderate/severe intensity headache within 48 hours, ability to function normally over 24 hours, and absence of a headache of any intensity within 24 hours post-dose. Patients used an e-diary to record the presence and severity of symptoms at the time of each qualifying prodrome event.

Ubrelvy is the first and only acute treatment for migraine that has demonstrated data in the prodrome phase in a Phase III, double-blind, placebo-controlled trial

See- "Ubrogepant for the treatment of migraine attacks during the prodrome: a phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial in the USA". Prof David W Dodick, MD, Prof Peter J Goadsby, MD, Prof Todd J Schwedt, MD, Prof Richard B Lipton, MD., et al. Published: November 15, 2023DOI:https://doi.org/10.1016/S0140-6736(23)01683-5.