Preventive fremanezumab sustains reductions in migraine days up to 2 years in real world

In the final analysis of the real-world PEARL study presented at EAN 2025, fremanezumab as a preventive treatment for chronic or episodic migraine halves the number of monthly migraine days (MMD) or more from 3 months onwards through 24 months.

“Sustained reductions in MMD from baseline were observed over the 24-month study period,” said Dr Verena Ramirez Campos, a neuroimmunologist at Teva Branded Pharmaceutical Products Research and Development, Inc., West Chester, Pennsylvania, US.

At 3 months after fremanezumab initiation, 58.1 percent of patients across the migraine spectrum experienced ≥50-percent reduction in MMD from a mean of 14.6 days at baseline. Over 55 percent of those who continued to receive fremanezumab achieved this outcome thereafter at seven subsequent follow-ups, and at the 24-month point, it was 55.7 percent. [EAN 2025, abstract EPR-039]

Adherence to scheduled fremanezumab injections within ±5 days during the observational period was at least 90 percent for each injection, except for the 13^th monthly injection (81.3 percent). The adherence rate for the 24^th injection scheduled for patients on monthly dosing was 95.4 percent.

“Findings from the final analysis of PEARL demonstrate that long-term fremanezumab is associated with sustained effectiveness and robust adherence,” concluded Ramirez Campos.

Real-world effectiveness

PEARL was a 24-month, prospective, observational, phase IV study to evaluate the effectiveness, safety, and tolerability of fremanezumab in adults with migraine across 11 European countries. [Cephalalgia 2023;43:3331024231214987]

A total of 1,140 patients were enrolled from real-world clinical practice, of whom 1,129 constituted the full analysis set (FAS) for evaluating effectiveness in the current analysis.

“This final analysis was conducted once all participants completed 24 months of follow-up,” said Ramirez Campos.

The primary endpoint was the proportion of patients with ≥50-percent reduction in average MMD during the 6 months following fremanezumab initiation. [Pain Manag 2021;11:647-654]

The final findings showed that 56.5 percent of patients with either migraine type achieved the primary endpoint, including 51.6 percent of chronic migraine (CM) patients and 66.3 percent of episodic migraine (EM) patients. Because the primary endpoint captured the effectiveness of fremanezumab at an earlier timepoint in the study, the final results were generally consistent with those described in the prior interim analyses. [EAN 2022, abstract EPR-035; MTIS 2022, poster PO-054; EAN 2023, abstract EPR-045; EAN 2024, poster EPV-312]

On a continuous scale, the mean change in MMD from baseline at 24 months was −9.4 days in the FAS, −10.7 days in CM patients, and −7.2 days in EM patients.

Real-world safety, tolerability

The safety and tolerability of fremanezumab prophylactic treatment for up to 2 years were also captured in the final analysis, which data covered all enrolled patients.

“Drug-related adverse events (AEs) were experienced by 33 percent of participants, and only 0.4 percent reported a serious drug-related AE,” said Professor Cristina Tassorelli from the Department of Brain and Behavioral Sciences, University of Pavia, Lombardy, Italy, in another presentation at EAN 2025. [EAN 2025, poster EPO-063]

The most common drug-related AE reported was injection site erythema in 8.6 percent of all enrolled patients.

“No new safety signals were observed despite the long duration of treatment,” concluded Tassorelli. “The safety and tolerability profile of fremanezumab in this final analysis is consistent with results from previously reported randomized controlled trials and the PEARL interim analyses.”

The two dosing options of fremanezumab are its unique aspect among the available calcitonin gene-related peptide monoclonal antibodies for migraine, and they were also utilized in PEARL. In the FAS, 14.1 percent of patients had ever been treated with fremanezumab 675 mg every 3 months.