Ubrelvy Shows Promise for Treating Prodromal Migraine Symptoms

Results from the phase 3 PRODROME trial (NCT04492020) published in Nature Medicine suggest that treatment with Ubrelvy 100 mg (ubrogepant; AbbVie, North Chicago, IL), a calcitonin gene-related peptide (CGRP) receptor antagonist, may effectively resolve common prodromal (premonitory) symptoms of migraine in adults when administered before the onset of headache, including photophobia, cognitive dysfunction, and phonophobia.

PRODROME was a randomized, double-blind, placebo-controlled crossover study which enrolled 477 individuals (mean age, 42.3 years; 87.7% female) with migraine who could reliably identify prodromal symptoms that predicted headache within 1 to 6 hours. Participants were treated for 2 qualifying prodrome events within a 60-day period, receiving both Ubrelvy 100 mg and placebo in randomized sequence. Exploratory end points included the absence of the 5 most common prodromal symptoms at multiple timepoints postdose, with outcomes assessed over 48 hours using electronic diary entries. Safety assessments included monitoring for treatment emergent adverse events (TEAEs).

Key results:

• Absence of photophobia 2 hours postdose was 19.5% with Ubrelvy vs 12.5% with placebo (OR, 1.72; 95% CI, 1.13 to 2.61).
• Absence of fatigue 3 hours postdose was 27.3% vs 16.8% (OR, 1.85; 95% CI, 1.17 to 2.92).
• Absence of neck pain 3 hours postdose was 28.9% vs 15.9% (OR, 2.04; 95% CI, 1.25 to 3.32).
• Absence of phonophobia 4 hours postdose was 50.7% vs 35.8% (OR, 1.97; 95% CI, 1.38 to 2.80).
• Absence of dizziness 24 hours postdose was 88.5% vs 82.3% (OR, 1.82; 95% CI, 1.00 to 3.30).
• Cognitive symptoms postdose improved as early as 1 hour for difficulty concentrating (8.7% vs 2.1%; OR, 4.26; 95% CI, 1.17 to 15.54) and at 6 hours for difficulty thinking (56.9% vs 41.8%; OR, 2.05; 95% CI, 1.14 to 3.71).
• The use of rescue medication was lower with Ubrelvy (21.7%) than placebo (39.4%) within 24 hours post-dose.
• No serious (TEAEs) were reported. The most common side effects were mild and included nausea, fatigue, and somnolence.

Source: Goadsby PJ, Ailani J, Dodick DW, et al. Ubrogepant for the treatment of migraine prodromal symptoms: an exploratory analysis from the randomized phase 3 PRODROME trial. Nat Med. Published online May 12, 2025. https://doi.org/10.1038/s41591-025-03679-7