A Review of Monoclonal Antibody Therapies and Other Preventative Treatments in Migraine

Abstract

Monoclonal antibodies targeting the calcitonin gene-related peptide pathway represent a new class of mechanism-specific, migraine-targeted therapies available for migraine prevention. To date, four monoclonal antibodies have demonstrated efficacy in phase II and III trials, significantly reducing migraine days per month versus placebo with rapid onset of action. While their efficacy may be considered similar to existing preventive options, their true value may lie in an improved tolerability profile, with high specificity and selectivity for the calcitonin gene-related peptide receptor or ligand reducing the potential for off-target binding and toxicity. The infrequent parenteral administration of these therapeutic proteins, and lack of requirement for dose titration, has potential to simplify treatment selection and use for clinicians and patients. However, the treatments have not yet been tested in real-world settings in patients with the range of comorbid conditions encountered in routine clinical practice, and longer-term data on safety, efficacy, and treatment persistence are required. If data from real-world settings can confirm the initial clinical trial findings, it is hoped that antibodies antagonizing the calcitonin gene-related peptide pathway will be able to improve quality of life for patients with episodic and chronic migraine, and help relieve the huge patient and societal burden of migraine. Novel treatments designed to target the specific pathophysiology of migraine could have an important place in future migraine management.

Effect of Galcanezumab Following Treatment Cessation in Patients With Migraine: Results From 2 Randomized Phase 3 Trials

“…The neuropeptide, calcitonin gene‐related peptide (CGRP), is implicated in the pathophysiology of migraine and is hypothesized to be involved in the release of inflammatory mediators and transmission of nociceptive information from intracranial blood vessels to the nervous system . CGRP or its receptor are targets for migraine preventive agents . Small molecule receptor antagonists and monoclonal antibodies (ie, galcanezumab, erenumab, fremanezumab), directed against either CGRP or its receptor, are under development or approved by the US Food and Drug Administration (FDA) for migraine prevention .…”

“…4 Oral preventive medications for migraine are available, but usage is frequently limited by adverse events (AE). 5 Thus, there is a medical need for new treatment options with improved tolerability.…”

“…6,7 CGRP or its receptor are targets for migraine preventive agents. 5,6 Small molecule receptor antagonists and monoclonal antibodies (ie, galcanezumab, erenumab, fremanezumab), directed against either CGRP or its receptor, are under development or approved by the US Food and Drug Administration (FDA) for migraine prevention. [8][9][10] Immunoglobulins of class G (IgG) have a half-life of approximately 3 weeks; 11 this can be exploited by drugs used as migraine preventive agents, which ideally should be administered infrequently and be long acting.…”

Foreword: The CGRP Pathway and Migraine Prevention: Reducing the Burden of Disease

“…Despite this severe unmet need, the current state of migraine therapy is expertly described by Professor Reuter . Migraine patients “desire to be migraine‐free, rapidly, and without side effects, to relieve pain and disability, and restore normal functioning.” Yet current preventative therapies are often hampered by poor efficacy or unwanted side effects, leading to poor adherence levels over time .…”

“…Excitingly, this was followed by the development of monoclonal antibodies (mAbs), of which there are now four (“umabs”), targeting either the CGRP receptor (erenumab) or the CGRP peptide (galcanezumab, eptinezumab, and fremanezumab). As highlighted by Professor Reuter, these novel migraine preventative therapies have the potential to shape the near future of migraine care. Phase III clinical trials have demonstrated the safety and efficacy of mAbs with a significant reduction in monthly migraine days and comparable adverse events to placebo, while, so far, one open‐label extension study suggests a continued effect at least to 15 months…”