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MINNEAPOLIS — For the millions who suffer from debilitating migraines, the wait for relief can feel endless. Traditional preventive medications often require weeks or months of daily use before patients experience meaningful benefits. Now, a series of clinical trials from a team of international researchers suggests a new medication called atogepant may offer something previously elusive in migraine prevention: rapid relief, potentially starting from day one.
Atogepant, taken orally once daily, belongs to a class of drugs called calcitonin gene-related peptide (CGRP) receptor antagonists. CGRP is a protein that plays a key role in migraine development by causing blood vessels to dilate and promoting inflammation in the brain. By blocking CGRP receptors, atogepant helps prevent this cascade of events that leads to migraine attacks.
The drug’s rapid onset of action represents a significant advance over conventional preventive treatments. Many standard medications, such as antidepressants or blood pressure drugs repurposed for migraine prevention, require careful dose titration and extended use before patients notice improvement. This slow ramp-up period often leads to treatment abandonment.
“With many current drugs to prevent migraine, it takes time to find the right dosage for the individual and it can take weeks or even months for it to be most effective,” explains Dr. Richard B. Lipton of Albert Einstein College of Medicine, lead author of the study published in the journal Neurology, in a statement. “Some people give up and stop taking the drugs before they reach this point. Plus, many people experience side effects with current treatments. Developing a drug that works both effectively and quickly is critical.”
Three-headed study on atogepant use
The research, funded by atogepant maker AbbVie, comprised three phase 3 trials named ADVANCE, ELEVATE, and PROGRESS. The trials evaluated atogepant’s effectiveness in preventing both episodic migraines (occurring 4-14 days per month) and chronic migraines (15 or more headache days monthly, with at least eight being migraines). The studies, involving approximately 1,250 participants across multiple countries, found that patients taking atogepant experienced significant improvements within the first four weeks of treatment, though the full trials lasted 12 weeks.
In the ADVANCE trial, only 12% of patients taking atogepant experienced a migraine on day one, compared to 25% of those on placebo. Similar patterns emerged in the ELEVATE (15% vs. 26%) and PROGRESS trials (51% vs. 61%). After adjusting for other factors affecting migraine rates, researchers found that atogepant reduced the likelihood of having a migraine by 61% in ADVANCE, 47% in ELEVATE, and 37% in PROGRESS.
Instant relief for migraine patients
The benefits extended beyond the first day. In the episodic migraine trials (ADVANCE and ELEVATE), patients taking atogepant averaged one fewer migraine day per week compared to less than half a day reduction with placebo. For chronic migraine patients in PROGRESS, the reduction was even more pronounced – about 1.5 fewer migraine days per week versus one day for placebo.
“Migraine is the second-leading cause of disability in the overall population and the leading cause of disability in young women,” notes Dr. Lipton, “with people reporting negative effects on their relationships, parenting, career and finances. Having a treatment that can act quickly and effectively addresses a key need.”
The study populations largely reflected typical migraine demographics, with women comprising approximately 87-89% of participants across the trials. Most participants were White, though the PROGRESS trial included a more diverse population with significant Asian representation. Average participant age ranged from 40-43 years.
Side effects were generally mild, with similar discontinuation rates between atogepant and placebo groups during the first four weeks. The most common adverse events included nausea, constipation, and fatigue.
Major upgrade for current treatments
The speed of atogepant’s action represents more than just convenience – it could fundamentally change how we approach migraine prevention. Based on prior research cited in the paper, patients consistently rank rapid onset of effect as a highly desired attribute for preventive treatments. The ability to experience benefits within days rather than months may help more patients persist with preventive therapy long enough to realize its full effects.
Just as the minutes feel like hours during a migraine attack, the weeks of waiting for preventive medications to work can feel like an eternity. With these promising results, that waiting game may finally be getting shorter.
Top Comments From Readers
“As a migraine sufferer, these results aren’t the breakthrough the drug company wants us to believe – a half day a week benefit compared to placebo? And the way it’s worded with the weirdly defined trials makes me think this is mostly a numbers game. … Feels like another pharmaceutical company trying to make a lot of money to me.”
“CGRP drugs are not a panacea. they are eye wateringly expensive, and have risks. small vessels are affected by this drug class – which means that people with circulatory disorders may be at risk when using this class; i have seen these complications in two patients. … this is a case where the information provided is true, but not fully accurate nor contextual.”
Paper Summary
Methodology
The researchers conducted three separate but related clinical trials, each lasting 12 weeks and comparing atogepant to a placebo. Participants kept detailed electronic diaries tracking their migraine days, symptoms, and ability to function. The trials used randomization and double-blinding, meaning neither patients nor researchers knew who received the actual drug versus placebo during the study. They measured outcomes including the number of migraine days, physical function, quality of life, and safety parameters. To qualify, participants needed at least a one-year history of migraine with onset before age 50.
Results
In all three trials, atogepant showed superiority to placebo starting from the first day. The odds of having a migraine on day one were significantly lower in the treatment groups. Weekly migraine days decreased more in treated patients, with benefits maintained throughout the first month. Quality of life measures improved as early as week one. The magnitude of benefit was similar across different patient populations, whether they had episodic or chronic migraine.
Limitations Overview
The study populations were predominantly female and White, particularly in the ADVANCE and ELEVATE trials, potentially limiting generalizability to other demographics. The trials excluded patients using opioids or barbiturates frequently for pain control and those who had failed more than four preventive treatments. The analysis focused only on the first four weeks of treatment, though the full trials lasted 12 weeks.
Discussion and Takeaways
The consistent results across three large trials provide strong evidence for atogepant’s rapid effectiveness in preventing migraines. The drug’s quick onset of action could help address a major limitation of existing preventive treatments. The benefits extended beyond just reducing migraine frequency to improving patients’ ability to function in daily life. The similar efficacy across different patient populations suggests broad applicability.
Funding and Disclosures
The studies were funded by AbbVie, the manufacturer of atogepant. Many study authors reported receiving consulting fees, research support, or other compensation from pharmaceutical companies including AbbVie, Allergan, Amgen, Eli Lilly, and others involved in migraine treatment. The trials were registered with ClinicalTrials.gov and received appropriate institutional review board approvals.
I suffer classic Migraine diagnosed by neurologists but my previous post explaining which foods to avoid that cause Migraine was deleted by moderation that require drugs to be the cure!
When you stop eating the following things your migraines will end, no more raisins, raisins cause the worst migraines. Do not drink your coffee to the bottom of the cup, the grinds at the bottom will cause migraines. Kefir causes migraine, some chapsticks cause migraine.
As a migraine sufferer, these results aren’t the breakthrough the drug company wants us to believe – a half day a week benefit compared to placebo? And the way it’s worded with the weirdly defined trials makes me think this is mostly a numbers game. People need to keep in mind that in these studies “significant” means “statistically significant”, “not meaningfully significant”. It’s interesting they don’t say that for some people the benefits are much much more. Feels like another pharmaceutical company trying to make a lot of money to me.
If you go on a strict carnivore diet, you’ll end your migraines. Worked for me.
CGRP drugs are not a panacea. they are eye wateringly expensive, and have risks. small vessels are affected by this drug class – which means that people with circulatory disorders may be at risk when using this class; i have seen these complications in two patients.
the idea that preventive drugs take months to work is inaccurate; in my experience the majority of patients are seeing preventive improvement in a couple of weeks, and doing so with cheap old meds. i’m an internist, who also has migraines, so i’m very motivated to improve them for myself and my patients both.
this is a case where the information provided is true, but not fully accurate nor contextual.