Migraine Treatment: From Symptomatic Relief to Targeted Therapy

  On March 31st, the latest announcement on the website of the Center for Drug Evaluation (CDE) revealed that the marketing application for Pfizer‘s Rimegepant Sulfate Orally Disintegrating Tablets has been accepted. This represents a significant breakthrough for the standardized treatment of migraine in China.

  Migraine is a complex, chronic neurovascular disorder. The mainstay of early clinical treatment was the triptan class of drugs, represented by zolmitriptan and rizatriptan. These drugs primarily act by agonizing 5-HT1B receptors, leading to a potent constriction of dilated cerebral blood vessels and inhibiting neuronal excitation.

  Based on migraine research, Calcitonin Gene-Related Peptide (CGRP) has been identified as a key mediator. CGRP is a 37-amino-acid neuropeptide. Its release increases during a migraine attack, causing vasodilation and promoting the release of inflammatory factors. This process triggers neurogenic inflammation and pain signal transmission, and is also associated with mood disorders such as anxiety and depression.

  CGRP small-molecule antagonists work by blocking the binding of CGRP to its receptor, thereby inhibiting the onset of migraines at the source. The first CGRP monoclonal antibody, erenumab, was approved in 2018. Subsequently, small-molecule CGRP antagonists (gepants) such as rimegepant, atogepant, ubrogepant, and zavegepant entered the market. Administered orally with a rapid onset of action, this class of drugs offers both acute and preventive treatment, establishing them as preferred treatment options for migraine.

  Currently, the pivotal role of CGRP in pain transmission is a major research focus. Researchers are actively exploring combination therapies involving gepants and other drugs. This signifies that the CGRP-targeted therapeutic field is poised for substantial market opportunities alongside considerable technical challenges.