Friedman Deborah I, Cohen Joshua M
Departments of Neurology and Neurotherapeutics and Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A.
Global Medical Affairs, Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, U.S.A.
Emerg Top Life Sci. 2020 Sep 8;4(2):179-190. doi: 10.1042/ETLS20200018.
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.
瑞美吉泮是一种全人源单克隆抗体（IgG2Δa），其靶向降钙素基因相关肽（CGRP），这是一种参与偏头痛病理生理学的关键神经肽。瑞美吉泮已获批用于成人偏头痛预防性治疗的季度和月度皮下给药。瑞美吉泮的3期临床开发项目旨在评估这种预防性治疗在不同患者群体中的疗效，包括那些难治性偏头痛患者。两项关键的为期12周的3期安慰剂对照研究，调查了瑞美吉泮在慢性偏头痛患者（HALO CM）和发作性偏头痛患者（HALO EM）中的季度和月度给药情况。在为期12周的FOCUS研究中，对难治性慢性或发作性偏头痛患者进一步探索了瑞美吉泮的疗效，该研究招募了之前对2 - 4类偏头痛预防性药物反应不佳的参与者。在一项为期12个月的长期研究（HALO LTS）中评估了瑞美吉泮的长期疗效，该研究招募了完成12周HALO研究的参与者和新参与者。在这些研究中，与安慰剂相比，每季度或每月给药的瑞美吉泮治疗可显著减少偏头痛天数、至少中度严重程度的头痛天数以及与偏头痛和头痛相关的残疾。长期使用瑞美吉泮治疗可见持续改善。对难治性偏头痛患者（伴有合并抑郁症、过度使用急性头痛药物以及同时使用其他偏头痛预防性药物的患者）的亚组分析表明，每季度或每月使用瑞美吉泮在这些人群中有效。正在进行的研究正在进一步探索瑞美吉泮在难治性偏头痛以及其他头痛和疼痛疾病中的潜在益处。
