Fremanezumab: a disease-specific option for the preventive treatment of migraine, including difficult-to-treat migraine

Abstract

Fremanezumab is a fully humanized monoclonal antibody (IgG2Δa) that targets calcitonin gene-related peptide (CGRP), a key neuropeptide involved in the pathophysiology of migraine. Fremanezumab is approved for quarterly and monthly subcutaneous dosing for the preventive treatment of migraine in adults. The phase 3 clinical development program for fremanezumab aimed to evaluate the efficacy of this preventive treatment across different patient populations, including those with difficult-to-treat migraine. Two pivotal 12-week, phase 3, placebo-controlled studies investigated quarterly and monthly dosing of fremanezumab in participants with chronic migraine (HALO CM) and episodic migraine (HALO EM). The efficacy of fremanezumab was further explored in individuals with difficult-to-treat chronic or episodic migraine in the 12-week FOCUS study, which enrolled participants who had previously experienced an inadequate response to 2–4 pharmacological classes of migraine preventive medications. The long-term efficacy of fremanezumab was assessed in a 12-month long-term study (HALO LTS), which enrolled participants completing the 12-week HALO studies and new participants. Across these studies, treatment with fremanezumab dosed quarterly or monthly provided significant reductions in the frequency of migraine days, headache days of at least moderate severity, and migraine- and headache-related disability compared with placebo. Sustained improvements were seen with long-term fremanezumab treatment. Subgroup analyses of participants with difficult-to-treat migraine (those with comorbid depression, overuse of acute headache medications, and concomitant use of other migraine preventive medications) demonstrated the effectiveness of quarterly or monthly fremanezumab in these populations. Ongoing studies are further exploring the potential benefits of fremanezumab in difficult-to-treat migraine and other headache and pain disorders.

Calcitonin Gene-Related Peptide (CGRP)-Targeted Monoclonal Antibodies and Antagonists in Migraine: Current Evidence and Rationale

“…Several phase II RCTs are underway assessing fremanezumab for treating patients with migraine and major depressive disorder, post-traumatic headache, and fibromyalgia [ 73 ]. RWD of fremanezumab after 6 months have revealed MMD reductions of − 7.7 and − 10.1 in patients with EM and CM, respectively [ 74 ].…”

Alpha-Calcitonin Gene Related Peptide: New Therapeutic Strategies for the Treatment and Prevention of Cardiovascular Disease and Migraine

“…Fremanezumab (TEV-48125) is a fully monoclonal IgG2 antibody that blocks CGRP signaling by binding to αand β-forms of CGRP to inhibit these ligands from interacting with the CGRP receptor (Hoy, 2018). Approved by the FDA and developed by Teva Pharmaceuticals, fremanezumab (commercial name Ajovy) is administered monthly or quarterly via a subcutaneous injection to prevent migraine attacks (Friedman and Cohen, 2020). In vitro studies found that fremanezumab inhibits CGRP-induced vasodilation of intracranial and abdominal arteries.…”

Tratamiento preventivo de la migraña con fremanezumab subcutáneo

“…• Uso concomitante de otros preventivos. El fremanezumab es eficaz y seguro en pacientes que toman otros preventivos (n = 1.110), siendo los más usados en los estudios la amitriptilina y el topiramato 46,49 . -Tasa de reversión de migraña crónica a migraña episódica.…”

“…-PRO (patient-reported outcomes). La puntuación de la escala MSQ (Migraine-Specific Quality of Life Questionnaire) y del índice HIT-6 (Headache Impact Test-6) mejoran significativamente respecto al grupo placebo 46 . -Calidad de vida.…”

“…-Calidad de vida. Los pacientes tratados con fremanezumab han mostrado mejorías significativas en la puntuación de todas las escalas aplicadas: MS-QoL (Multiple Sclerosis Quality of Life), EQ-5D-5L (EuroQol 5 Dimensions 5 Levels), PGIC (Patients' Global Impression of Change) y WPAI:GH (Work Productivity and Activity Impairment Questionnaire: General Health) (n = 1.121) 46,51,52 . Asimismo, los -Una quinta investigación (n = 772) no ha constatado diferencias de eficacia si se realiza switching entre las dos pautas de fremanezumab 66 .…”