What Is Atogepant?
Atogepant is an FDA-approved medication for the preventive treatment of episodic and chronic migraine. It is an oral, small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist. CGRP is a neurotransmitter involved in pain pathways, and blocking its receptor can help prevent migraine attacks. Atogepant is part of the gepant family of drugs, representing a second-generation option for migraine prevention.
In clinical trials, atogepant has been studied at doses up to 60 mg daily. It is currently approved for individuals experiencing at least 4 monthly migraine days, with or without medication overuse. Beyond its approved uses, atogepant continues to be investigated for its potential in other migraine-related conditions, including specific types like menstrual migraine and migraine with aura.
Uses and Conditions Under Study
Atogepant is primarily studied for the prevention of migraine, a neurological disease characterized by moderate to severe headaches, often accompanied by throbbing, nausea, vomiting, and sensitivity to light and sound. CGRP, which atogepant targets, is believed to play a key role in these symptoms by affecting afferent pathways involved in pain and hypersensitization.
The drug has been extensively investigated across various migraine presentations:
- Episodic and Chronic Migraine: Atogepant is approved for the preventive treatment of both episodic migraine (10 trials) and chronic migraine (8 trials). These conditions are defined by the frequency of migraine days per month.
- General Migraine Studies: A total of 8 trials have focused on migraine without specifying episodic or chronic types, further exploring the drug's effectiveness and safety across the broader migraine population.
- Specific Migraine Subtypes: Atogepant has also been studied for more specific migraine conditions, including Menstrual Migraine (MM) (1 trial), Migraine With Aura (1 trial), and Migraine Without Aura (1 trial). These investigations aim to understand the drug's utility in diverse patient groups.
- Migraine Prophylaxis: Several trials (2 trials) specifically examine atogepant for migraine prophylaxis, or prevention, reinforcing its role in reducing migraine frequency.
Additionally, one study assessed how atogepant moves through the body in healthy adult lactating female participants, providing important safety information for this population.
Dosing
Atogepant is available as an oral tablet. Clinical trials have investigated various strengths and dosing regimens to determine its safety and effectiveness for migraine prevention.
For adults, common doses studied include:
- Atogepant 60 mg: This dose has been studied as a once-daily (QD) regimen for both chronic migraine and episodic migraine prevention. Some trials specifically evaluated 60 mg daily for 3 months.
- Atogepant 30 mg: This strength has been studied as both a once-daily (QD) and twice-daily (BID) regimen.
- Atogepant 10 mg: This lower strength has also been investigated as a once-daily (QD) dose.
In addition to single-agent studies, atogepant has been evaluated in combination with other treatments. For example, studies have assessed the drug-to-drug interaction and coadministration of atogepant with ubrogepant, another approved migraine medication.
Investigational pediatric doses have also been explored across different age groups. These include "Atogepant Dose A" for adolescents (12-17 years) and "Atogepant Dose B" for younger children (6-11 years), with both high and low dose regimens being tested in double-blind treatment periods and open-label pharmacokinetic substudies.
Side Effects
Like all medications, Atogepant can cause side effects. In clinical trials for migraine prevention, certain side effects were reported more frequently by patients taking Atogepant compared to those taking a placebo. It is important to note that not everyone experiences these effects, and their severity can vary.
- The most common side effect was constipation, affecting 10.4% of patients taking Atogepant, compared to 2.9% of patients receiving a placebo. This finding is based on data from two trials involving 674 patients in the Atogepant treatment arm.
- Nausea was also a frequently reported side effect, experienced by 8.3% of patients on Atogepant, while 3.4% of those on placebo reported nausea. This data also comes from two trials with 674 patients in the Atogepant group.
- Nasopharyngitis, which includes symptoms similar to a common cold, occurred in 4.5% of patients taking Atogepant, compared to 2.2% of those on placebo. This was observed in one trial with 639 patients on Atogepant.
- An increase in blood creatine phosphokinase, an enzyme that can indicate muscle activity, was seen in 2.3% of Atogepant patients, versus 1.1% of placebo patients, in one trial with 639 patients.
- Little Rock, Arkansas (5 sites)
- Miami, Florida (4 sites)
- Austin, Texas (4 sites)
- Nashville, Tennessee (4 sites)
- Anaheim, California (3 sites)
- Oceanside, California (3 sites)
- Greensboro, North Carolina (3 sites)
- Papillion, Nebraska (3 sites)
- Bountiful, Utah (3 sites)
- Salt Lake City, Utah (3 sites)
Currently Recruiting Trials
Researchers are actively seeking participants for several clinical trials involving atogepant, a medication for migraine prevention. These studies aim to further understand its effectiveness, safety, and how it compares to other treatments across different patient populations, including adolescents.
One notable study, "Comparative Effectiveness of Migraine Preventive Medications: The APT Comparison Study" (NCT06972056), is a Phase 4 trial sponsored by Mayo Clinic. It seeks to enroll 1335 participants to compare atogepant with two established migraine preventive medications, topiramate and propranolol, evaluating which one works better and is more tolerable for individuals with migraine.
AbbVie is sponsoring multiple Phase 3 trials focused on pediatric populations. "A Study of Oral Atogepant Tablets to Assess Adverse Events and Change in Disease Activity To Prevent Migraine in Participants Aged 12 to 17 Years" (NCT06810505) is enrolling 420 adolescents with chronic migraine to evaluate adverse events and changes in disease activity. Another study, "Long-term Extension Study to Assess Adverse Events of Oral Atogepant Tablets in Pediatric Participants (6 to 17 Years of Age) With Migraine" (NCT05707949), is a long-term safety assessment for up to 650 children and adolescents. Additionally, "A Study to Assess the Adverse Events and Change in Disease Activity of Oral Atogepant Tablets in Pediatric Participants (6-17 Years of Age) With Episodic Migraine" (NCT05711394) is recruiting 450 pediatric participants with episodic migraine to assess safety and disease activity changes.
For adult participants, AbbVie is also conducting a Phase 3 study (NCT06241313) to assess the safety and efficacy of atogepant in 1300 adults with migraine. A large post-marketing study (NCT06603558) is underway in Korea, aiming to enroll 3000 adult participants with chronic or episodic migraine to assess the real-world safety and effectiveness of oral atogepant.
Other studies include "Neurophysiological and Biomolecular Effects of Atogepant in Episodic Migraine" (NCT06882122), an observational study by IRCCS National Neurological Institute "C. Mondino" Foundation, which is recruiting 30 participants to examine neurophysiological and biochemical changes induced by atogepant in high-frequency episodic migraine. The Cleveland Clinic is also conducting an observational cohort trial (NCT06212661) involving 200 participants to study the effects of CGRP inhibitors, including atogepant, on lower urinary tract symptoms and bladder/pelvic pain in individuals with migraine.
Where to Participate
Clinical trials for atogepant are broadly accessible across the United States, with study sites located in 30 states, encompassing 70 cities and a total of 132 individual locations. This wide geographic reach aims to make participation convenient for a diverse group of patients.
Top recruiting locations include:
Eligibility for these studies generally includes individuals of all genders, with an age range from 6 to 75 years. It is important to note that these trials are not seeking healthy volunteers; participants must have a diagnosed condition relevant to the study, such as migraine. Children are eligible to participate in specific trials designed for pediatric populations.
Development Timeline
The journey of atogepant began on July 28, 2016, with its first clinical trial. Since then, the development program has expanded significantly, with the latest trial projected to conclude in May 2025. A total of 26 trials have been conducted or are ongoing, involving over 15,360 participants.
Early in its development, atogepant was explored for conditions such as IBS-C and hyperphosphatemia. However, the focus quickly shifted and broadened, with a significant emphasis on migraine prevention. The pipeline expanded to include various migraine-related conditions, such as Migraine, Menstrual Migraine, Migraine Disorder, Migraine Prophylaxis, and specific types like Migraine With Aura and Migraine Without Aura. Later, the scope further diversified to investigate potential effects on conditions like Overactive Bladder, Bladder Pain Syndrome, and Interstitial Cystitis.
AbbVie has been the primary driver of atogepant's development, sponsoring 14 trials, with Allergan also playing a significant role in 7 trials. The majority of studies have progressed to advanced stages, with 16 trials reaching Phase 3, indicating a strong commitment to establishing the drug's efficacy and safety for its target indications. Two Phase 4 trials are also underway, focusing on post-marketing surveillance and comparative effectiveness.