Fremanezumab Reduces Acute Medication Use and Migraine Symptoms in Episodic Migraine, Phase 2b/3 Trial Shows

Muneto Tatsumoto, MD, PhD

(Credit: ResearchGate)

Fremanezumab (Ajovy; Teva Pharmaceuticals), an FDA-approved monoclonal antibody targeting migraine prevention, significantly reduced acute medication use and improved migraine-related symptoms in patients with episodic migraine (EM), according to recent findings published in Headache from a phase 2b/3 trial conducted in Japan and Korea.¹ The study results underscored fremanezumab’s role in not only preventing migraine attacks but also in reducing the reliance on acute headache medications and mitigating associated symptoms.

The study evaluated exploratory end points in 357 patients with EM who were randomized to receive monthly or quarterly fremanezumab or placebo. Over 3 months, fremanezumab led to notable reductions in the number of days requiring acute headache medication, migraine-specific medication use, and the frequency of nausea, vomiting, photophobia, and phonophobia.

Conducted by lead author Muneto Tatsumoto, MD, PhD, group manager at Canon Marketing Japan, and colleagues, the trial was a multicenter, randomized, double-blind, placebo-controlled study assessing the impact of fremanezumab on EM. Patients received monthly or quarterly subcutaneous injections of the calcitonin gene-related peptide (CGRP)-targeting medication or placebo to maintain blinding. Exploratory end points included the monthly number of days with acute headache medication use, migraine-specific medication use, and the presence of migraine-associated symptoms.

Key findings showed that compared with placebo, fremanezumab significantly reduced the monthly days of acute medication use by 2.81 days (95% CI, -3.52 to -2.11; P <.001) for monthly dosing and by 2.79 days (95% CI, -3.50 to -2.08; P <.001) for quarterly dosing. Similar improvements were observed in the use of migraine-specific medications, with both dosing schedules reducing usage by 2.63 days (95% CI, -3.31 to -1.95; P <.001).

Additionally, fremanezumab reduced the number of days with nausea or vomiting by 1.09 days (95% CI, -1.60 to -0.58; P <.001) for monthly dosing and 1.37 days (95% CI, -1.88 to -0.86; P <.001) for quarterly dosing. The frequency of photophobia and phonophobia also decreased by 1.22 days (95% CI, -1.80 to -0.65; P <.001) and 1.64 days (95% CI, -2.22 to -1.06; P <.001) with monthly and quarterly dosing, respectively. Overall, these findings may inform treatment strategies for patients with EM in need of effective, preventive solutions.

READ MORE: Case Report Demonstrates Potential of CGRP-Targeting Medication to Treat Post-Subarachnoid Hemorrhage Headaches

An additional real-world study published in The Journal of Headache and Pain showed that fremanezumab at doses of 675 mg, administered quarterly, may offer long-term benefits for patients with EM and chronic migraine (CM), with 70.4% of patients experiencing effective headache reduction over 2 years.² These results build on prior evidence from studies that demonstrated fremanezumab’s efficacy in reducing monthly migraine days and migraine-related symptoms.

The single-center observational study tracked 28 patients over 24 months, assessing headache frequency and adherence to treatment. Among the 27 patients who continued beyond the first injection, nearly half remained on fremanezumab until study completion. Sustained improvements allowed 25.9% of patients to discontinue treatment, while insufficient effectiveness led to discontinuation in 22.2% of cases.

The study included patients aged at least 15 years with EM or CM who initiated fremanezumab 675 mg quarterly dosing between November 2021 and June 2022. Headache frequency and severity were recorded using headache diaries over 24 months. Reasons for treatment discontinuation were documented through follow-up medical records. Of the 27 patients who continued fremanezumab after the first injection, 70.4% (n = 19) experienced effective treatment outcomes. By study termination, 44.4% (n = 12) had remained on the medication for the full 2 years. Among those who consistently updated monthly headache calendars (n = 7), mean changes in monthly migraine days (MMD) from baseline were -2.2 at three months, -1.8 at 12 months, and -1.6 (SD = 3.0) at 2 years.

Notably, 25.9% (n = 7) discontinued treatment because of sustained improvement, highlighting fremanezumab’s potential to facilitate medication cessation in well-responding patients. In contrast, 22.2% (n = 6) stopped because of insufficient effectiveness. Other reasons for discontinuation included injection-site erythema (3.7%), pregnancy (3.7%), and loss to follow-up (3.7%). Although clinical trials confirmed its short-term benefits, this real-world study provided insight into long-term adherence and treatment outcomes.

REFERENCES
1. Tatsumoto M, Ishida M, Iba K, et al. Effects of fremanezumab on migraine-associated symptoms and medication use in Japanese and Korean patients with episodic migraine: Exploratory endpoint analysis of a multicenter, randomized, double-blind, placebo-controlled trial. Headache. 2025;65(3):399-406. doi:10.1111/head.14810
2. Yoshida S, Imai N, Keicho M, et al. Efficacy and continuability of 675 mg fremanezumab administration over 2 years. J Headache Pain. 2025;26(1):51. Published 2025 Mar 11. doi:10.1186/s10194-025-01994-5