Research Summary

Galcanezumab Converts Chronic to Episodic Migraine Frequency in Long-Term Phase 3 REGAIN Study

Edited by:
Ashton L. Stahl

Key Highlights

  • Galcanezumab significantly increased rates of conversion from chronic to episodic migraine versus placebo during the double-blind phase.
  • Nearly two-thirds of treated patients shifted to episodic migraine frequency over 12 months.
  • Sustained reductions to low- and very low-frequency episodic migraine were observed in a substantial subset of patients.

New findings from a post-hoc analysis of the phase 3 REGAIN trial show that galcanezumab was associated with meaningful reductions in migraine frequency among adults with chronic migraine. The analysis, published in The Journal of Headache and Pain, focused on the proportion of patients who converted from chronic migraine frequency to episodic migraine frequency during both short- and long-term treatment.

REGAIN was a randomized, double-blind, placebo-controlled phase 3 study followed by a 9-month open-label extension. Adults aged 18 to 65 years old with chronic migraine, defined by ICHD-3β criteria, were randomized 2:1:1 to monthly placebo, galcanezumab 120 mg with a 240-mg loading dose, or galcanezumab 240 mg for 3 months. Patients entering the open-label extension received galcanezumab with flexible dosing. This post-hoc analysis assessed the proportion of patients who shifted from chronic migraine to episodic migraine frequency, defined as fewer than 15 headache days per month or fewer than 8 migraine headache days per month, for at least 3 consecutive months.

Study Findings

At baseline, patients experienced a mean of 19.4 migraine headache days and 21.4 total headache days per month. During the 3-month double-blind period, 31.5% of patients treated with pooled galcanezumab maintained episodic migraine frequency across all 3 months, compared with 19.8% of placebo-treated patients (P < .001). Similar statistically significant differences favoring galcanezumab were observed at individual monthly time points.

Across the full 12-month study period, 65.1% of patients treated with galcanezumab shifted from chronic to episodic migraine frequency for at least 3 consecutive months. Among these patients, 44.2% achieved low-frequency episodic migraine and 21.5% achieved very low-frequency episodic migraine. When sustained through the final study visit, 55.0% maintained episodic migraine frequency, including 33.4% with low-frequency and 13.9% with very low-frequency episodic migraine.

Clinical Implications

According to the study authors, the ability to convert patients from chronic to episodic migraine frequency represents a clinically relevant outcome, as lower migraine frequency is associated with reduced disability and healthcare burden. The findings suggest that long-term preventive treatment with galcanezumab may help a substantial proportion of patients achieve and maintain episodic migraine frequency over time.

Expert Commentary

“Results from this 12-month phase 3 study suggest that galcanezumab for the preventive treatment of [chronic migraine] may lead to substantial proportions of patients shifting to [episodic migraine] frequency for ≥3 consecutive months,” the researchers concluded.

Reference:
Diener HC, Day KA, Lipsius S, Aurora SK, Hindiyeh NA, Detke HC. Shift from chronic to episodic migraine frequency in a long-term phase 3 study of galcanezumab. J Headache Pain. 2025;26:26. doi:10.1186/s10194-025-01956-x