Ubrogepant effective in halting migraine in prodromal stage

A migraine is a common neurological disease that is characterized by most notably a throbbing, pulsing headache on one side of the head. About 12% of Americans have this genetic disorder. Research shows that it’s the sixth most disabling disease in the world. Ubrogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist that is approved for acute treatment of migraine.

A new trial published in The Lancet, suggests that in the earliest phase of a migraine attack Ubrogepant (Ubrelvy) halted migraine attacks during the prodrome better than placebo in a phase III trial

Researchers conducted a phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial “PRODROME “of ubrogepant 100 mg conducted at 75 research centres and headache clinics in the USA. Eligible participants were adults aged 18–75 years who had at least a 1-year history of migraine with or without aura and a history of two to eight migraine attacks per month with moderate to severe headache in each of the 3 months before screening. Eligible participants were randomly assigned (1:1) to either receive placebo to treat the first qualifying prodrome event and ubrogepant 100 mg to treat the second qualifying prodrome event or to receive ubrogepant 100 mg to treat the first qualifying prodrome event and placebo to treat the second qualifying prodrome event.

The primary endpoint was absence of moderate or severe intensity headache within 24 h after study-drug dose; efficacy analyses were conducted with the modified intention-to-treat (mITT) population, defined as all randomly assigned participants with at least one headache assessment within 24 h after taking the study drug during the treatment period.

The key findings of the study are

• Between Aug 21, 2020, and April 19, 2022, 518 participants were randomly assigned to double-blind crossover treatment.

• The safety population included 480 participants and the mITT population included 477 participants; 421 (88%) of 480 participants were female and 59 (12%) were male.

• Absence of moderate or severe headache within 24 h after a dose occurred after 190 (46%) of 418 qualifying prodrome events that had been treated with ubrogepant and after 121 (29%) of 423 qualifying prodrome events that had been treated with placebo (odds ratio 2•09, 95% CI 1•63–2•69; p<0•0001).

• Adverse events that occurred within 48 h after study-drug administration were reported after 77 (17%) of 456 qualifying prodrome events that had been treated with ubrogepant and after 55 (12%) of 462 events that had been treated with placebo.

Researchers concluded that “Ubrogepant was effective and well tolerated for the treatment of migraine attacks when taken during the prodrome.”

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