Atogepant Treatment Reduces Migraine Symptoms As Early As Day 1

Atogepant, an oral calcitonin gene-related peptide receptor antagonist, effectively reduces migraine frequency and improved functional outcomes as early as the first week of treatment, according to study findings published in Neurology.

Researchers analyzed 3 phase 3 trials: ADVANCE (Clinicaltrials.gov Identifier: NCT03777059), ELEVATE (Clinicaltrials.gov Identifier: NCT04740827), and PROGRESS (Clinicaltrials.gov Identifier: NCT03855137), to investigate atogepant for the preventive treatment of episodic migraine and chronic migraine. The researchers for the trials, randomized, double-blind, and placebo-controlled, enrolled participants aged 18 to 80 years with a ≥1-year history of migraine.

ADVANCE and ELEVATE targeted patients with episodic migraine with 4 to 14 monthly migraine days (MMDs), with ELEVATE focusing on those unresponsive to prior preventive treatments. PROGRESS focused on chronic migraine, characterized by ≥15 headache days and ≥8 MMDs.  A total of 910, 315, and 778 participants were randomly assigned in ADVANCE, ELEVATE, and PROGRESS, respectively, and all 3 trials evaluated atogepant 60 mg once daily.

The modified intent-to-treat (mITT) population included:

Participants treated with atogepant experienced a noticeable reduction in migraine days, beginning as early as day 1. The odds ratios for atogepant vs placebo were:

• ADVANCE: 0.39 (95% CI, 0.23-0.67; P =.0006)
• ELEVATE: 0.53 (95% CI, 0.29-0.94; P =.031)
• PROGRESS: 0.63 (95% CI, 0.43-0.93; P =.021)

Reductions in weekly migraine days were evident by week 1 and sustained through week 4. The least-squares mean differences (LSMDs) from placebo at week 1 were:

• ADVANCE: −0.74 (95% CI, −0.96 to −0.51; P <.0001)
• ELEVATE: −1.07 (95% CI, −1.37 to −0.76; P <.0001)
• PROGRESS: 0.85 (95% CI, −1.17 to −0.53; P <.0001)

Similar trends were observed for MMDs during the first 4 weeks, with LSMDs of −2.35 (ADVANCE), −3.07 (ELEVATE), and −2.43 (PROGRESS) compared with placebo (all P <.0001).

Improvements in the Activity Impairment in Migraine-Diary scores were observed as early as week 1. The performance of daily activities domain showed LSMDs of −4.22 in ADVANCE, −6.76 in ELEVATE, and −5.83 in PROGRESS at week 1 (all P <.0001).

Similarly, physical impairment scores improved significantly across all trials. European Quality-of-Life 5-Dimension 5-Level scores, which measure self-rated health, improved as early as weeks 1 to 2.

Atogepant was well tolerated, with treatment-emergent adverse events (TEAEs) reported in 36.4% of participants in ADVANCE, 33.3% in ELEVATE, and 41.0% in PROGRESS. Most TEAEs were mild to moderate in severity, consistent with previous 12-week analyses.

Study limitations included a sample size that was mostly women and White and the exclusion of frequent opioid/barbiturate users or those resistant to preventive treatments.

“The analyses reported here demonstrate the early efficacy and functional improvements of atogepant and address a key unmet need of providing preventive treatment options with early benefits across the spectrum of migraine disease state severity,” the researchers concluded.

This research was supported by AbbVie. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.