Trial Report Ubrogepant for the treatment of migraine prodromal symptoms: an exploratory analysis from the randomized phase 3 PRODROME trial, 2025, Goadsby et al

Ubrogepant for the treatment of migraine prodromal symptoms: an exploratory analysis from the randomized phase 3 PRODROME trial

Peter J. Goadsby, Jessica Ailani, David W. Dodick, Amaal J. Starling, Chengcheng Liu, Yingyi Liu, Sung Yun Yu, Jonathan H. Smith, Elimor Brand-Schieber & Joel M. Trugman

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Abstract
PRODROME was a phase 3, placebo-controlled, double-blind crossover trial evaluating whether ubrogepant 100 mg, a calcitonin gene-related peptide receptor antagonist, dosed during the premonitory (prodromal) phase of migraine, prevented development of headache and resolved prodromal symptoms. Qualifying prodromal events were defined as attacks with symptoms in which the participant was confident headache would follow within 1–6 h. Of 1,087 screened participants, 477 formed the efficacy analysis population.

Outcomes were collected across 48 h showing, for example, at 2 h post-dose, absence of photophobia in 19.5% and 12.5% of ubrogepant- and placebo-treated events, respectively (odds ratio (OR) = 1.72 (95% confidence interval (CI) = 1.13–2.61)); at 3 h post-dose, absence of fatigue occurred in 27.3% and 16.8% (OR = 1.85 (95% CI = 1.17–2.92)) and absence of neck pain in 28.9% and 15.9% (OR = 2.04 (95% CI = 1.25–3.32)) of events; at 4 h post-dose, absence of phonophobia in 50.7% and 35.8% (OR = 1.97 (95% CI = 1.38–2.80)) of events; and at 24 h post-dose, absence of dizziness in 88.5% and 82.3% (OR = 1.82 (95% CI = 1.00–3.30)) of events.

At 1 h and 6 h post-dose, respectively, absence of difficulty concentrating occurred in 8.7% and 2.1% (OR = 4.26 (95% CI = 1.17–15.54)) and absence of difficulty thinking occurred in 56.9% and 41.8% (OR = 2.05 (95% CI = 1.14–3.71)) of events.

Treatment with ubrogepant during the prodromal phase may ameliorate common prodromal symptoms, with improvements possibly as early as 1 h post-dose.

Link | PDF (Nature Medicine) [Open Access]

 

Nature News: 'Migraine drug is first to tackle debilitating early symptoms' [Paywall]

"Scientists have shown that a drug approved to treat migraine headaches can also alleviate debilitating non-headache symptoms, such as fatigue, brain fog and blinding light sensitivity, that occur as the migraine is starting.

The drug — called ubrogepant — is already known to stop the onset of a full-blown migraine attack in some people if they take it when the headache begins. But a phase III clinical trial, described in Nature Medicine on 12 May1, shows that it can also tackle the ‘prodrome’ symptoms that arrive hours or even days earlier."

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"But the “effect sizes were small” and never more than 15 percentage points compared with the placebo, points out Gregory Dussor, a neuroscientist and migraine specialist at the University of Texas at Dallas. For example, 27% of participants who took ubrogepant reported an absence of fatigue, compared with 17% who took the placebo. Dussor suggests this modest improvement is because the class of drugs to which ubrogepant belongs is a “life-changing therapeutic” for a minority of people — perhaps only one in five, according to some studies. It makes little difference to others, so its effect for that minority “gets diluted in the data”."

 

I have a monthly injection of Ajovy (similar type of therapy) and it is remarkable the difference. Not only to my migraine frequency and severity but also to my balance, pain, fatigue etc. These types of interventions are life changing. They move migraine management from coping to prevention. I refer patients over to the Walton Centre weekly.

Please do look into monoclonal antibody treatment for migraine if you have severe headaches/migraine. GPs can refer to tertiary headache clinics.