The FDA-approved CGRP-targeting monoclonal antibody fremanezumab (Ajovy; Teva Pharmaceuticals) has demonstrated sustained long-term efficacy in migraine prevention, according to comprehensive real-world data from the phase 4 PEARL study presented at the 11th Congress of the European Academy of Neurology in Helsinki.
PEARL Study Confirms Two-Year Effectiveness
The Pan-European Real-World study evaluated 1,140 patients with chronic or episodic migraine over a 24-month period, representing one of the largest real-world assessments of CGRP-targeting therapy. Of the 1,129 patients included in the effectiveness analysis, 33.1% had episodic migraine and 66.9% had chronic migraine, with 87.2% being female.
The study met its primary endpoint, with 66% of episodic migraine patients and 51.6% of chronic migraine patients achieving at least a 50% reduction in Monthly Migraine Days during the first six months of treatment. Importantly, benefits were observed early in the treatment course and sustained throughout the entire 24-month period.
"Over the last two years, we have observed the benefit of fremanezumab for sustained migraine prevention and its positive impact on patient outcomes," said Messoud Ashina, MD, PhD, DMSc, director of the Human Migraine Research Unit at the Danish Headache Center. "The PEARL study has provided valuable insight, not only into the pivotal role that fremanezumab can play in migraine prevention, but also in the importance of real-world studies in helping build our knowledge and shape clinical practice."
Significant Reduction in Acute Medication Use
Complementary findings from a phase 2b/3 trial conducted in Japan and Korea, published in Headache, demonstrated fremanezumab's impact beyond migraine frequency reduction. The multicenter, randomized, double-blind, placebo-controlled study evaluated 357 patients with episodic migraine over three months.
The study, led by Muneto Tatsumoto, MD, PhD, group manager at Canon Marketing Japan, showed that fremanezumab significantly reduced 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 compared to placebo.
Migraine-specific medication use was similarly reduced by 2.63 days (95% CI, -3.31 to -1.95; P <.001) for both dosing schedules. The treatment also significantly decreased migraine-associated symptoms, reducing days with nausea or vomiting by 1.09 days for monthly dosing and 1.37 days for quarterly dosing, while photophobia and phonophobia decreased by 1.22 days and 1.64 days respectively.
High Treatment Adherence and Sustained Benefits
Real-world evidence demonstrates exceptional treatment adherence, with over 75% (854 of 1,129) of patients in the PEARL study completing the full 24-month duration. A separate single-center observational study tracking 28 patients over 24 months found that 70.4% of patients experienced effective treatment outcomes with fremanezumab 675 mg administered quarterly.
Notably, 25.9% of patients in the observational study discontinued treatment due to sustained improvement, highlighting fremanezumab's potential to facilitate medication cessation in well-responding patients. Among patients who consistently maintained headache calendars, mean changes in monthly migraine days from baseline were -2.2 at three months, -1.8 at 12 months, and -1.6 at two years.
Pediatric Expansion Under Review
Teva Pharmaceuticals is seeking to expand fremanezumab's indication to include pediatric and adolescent patients aged 6-17 years weighing 45 kilograms or more. The FDA formally accepted the company's supplemental new drug application in April, supported by data from the phase 3 SPACE study.
The SPACE trial, comprising 237 pediatric patients with less than 14 headache days per month, demonstrated fremanezumab's superiority over placebo with a statistically significant reduction in monthly migraine days (-2.5 vs -1.4; P = .0210) and monthly headache days (-2.6 vs -1.5; P = .0172) over 12 weeks. Additionally, 47.2% of patients achieved at least a 50% response rate compared to 27.0% on placebo (P = .0016).
Safety Profile Remains Consistent
Throughout these studies, fremanezumab maintained a safety and tolerability profile consistent with previous randomized controlled trials. In the observational study, discontinuation due to adverse events was minimal, with only 3.7% stopping due to injection-site erythema.
Since its 2018 FDA approval as one of the first antibodies targeting the CGRP pathway, fremanezumab has been extensively studied across various contexts. A 2024 real-world study published in Cephalalgia found no wearing-off effect from the medication, with patients treated with 225 mg showing no difference in migraine days during weeks 2 and 4 of treatment.
