Atogepant: the chief oral drug developed specifically for prophylactic treatment of episodic migraine

Introduction Almost 1 billion individuals worldwide are thought to suffer from migraine, a common neurological condition that primarily affects women1. Globally, migraine accounts for the second-highest share of years spent living with a handicap1,2. Individuals suffering from migraine frequently experience interictal signs, like anxiety and avoidance of activities, which further diminish their life qualities2. Over 10% of people suffer from migraine worldwide. It is 3 times more prevalent in women as compared with men. People of the age group 20–50 years are the prime patients of this disease. According to a survey conducted in the United States, 6% of men and 17% of women suffer from migraine symptoms3. The lack of availability of a comprehensive approach results in the refractoriness and relapse of a episodic migraine in patients who show poor response to available medication. Interventional procedures may be needed in such patients suffering from refractory migraine. These include invasive neuromodulation and nerve blocks4. Large fluctuation and incidence of migraine episodes are frequent in migraine sufferers. Unrestrained migraine is linked to a lower level of well-being and a reduced capacity for everyday tasks. Fewer than 30% of patients with migraine who have moderate to severe disability from their condition and 4 or more migraine days per month report using a prescription to avoid migraines1. Atogepant: a calcitonin gene-related peptide receptor antagonist A small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist called “atogepant” has been permitted by the US Food and Drug Administration (FDA) to treat recurrent migraines prophylactically. It is the first oral drug created exclusively for the migraine prevention process. Atogepant greatly decreased mean monthly migraine days (MMDs) in two 12-week phase 2b/3 and phase 3 (ADVANCE) clinical trials compared with placebo. It also raised the ratio of participants who experienced a 50% or more decrease in MMDs2. Application and evidence of atogepant benefit in the treatment of migraine The trigeminovascular system releases CGRP while a migraine attack is occurring. It has strong vasodilation effects and stimulates ganglionic glial cells to discharge nitric oxide and proinflammatory cytokines5. In addition, by degranulation of mast cells, CGRP induces long-lasting proinflammatory activation of trigeminal pain receptors. This established process represents one of the many probable migraine pain routes5. Atogepant prevents the development of migraine by attaching to the CGRP receptor on the trigeminal nerve in the brain. Inhibition of the CGRP receptor can avoid or lessen migraine episodes and their intensity5. Atogepant is safe, well-tolerated, and effective for the prevention of migraines, according to the findings of a 52-week open-label, randomized trial of once-daily oral atogepant 60 mg. The majority of treatment emergent advance events ranged in intensity from mild to moderate, and none was severe6. All through the course of the trial, lab measurements in patients who received atogepant did not alter clinically meaningfully from their baseline values, providing further proof of atogepant’s safety. Changes in laboratory analytes did not cause any participants to stop the trial or experience any severe harmful events6. There were no liver health problems associated with atogepant therapy. None of the subjects had any instances of what might be Hy’s law6. Therapeutic advances of atogepant in migraine treatment Although CGRP was first postulated to contribute to the pathogenesis of migraine in the 1980s, medicines that target the CGRP pathway through the CGRP ligand or receptor have just recently been licensed7. The gepants—small-molecule receptors blockers (ubrogepant, rimegepant, and atogepant)—and large-molecule antibodies (erenumab, eptinezumab, fremanezumab, and galcanezumab)—are 2 categories of drugs that target the CGRP pathway. A novel avenue to particularly target migraines was established by the CGRP medicines. For the cure of migraines, Atogepant, a CGRP receptor antagonist, was given the FDA’s approval. It provides patients with an alternative treatment to injectable or intravenous monoclonal antibody therapies as well as a substitute for poorly tolerated, nonspecific migraine medicines7. Recommendations Although atogepant serves as an effective treatment for migraines, it is yet to show results for chronic or resistant migraine sufferers. Thus, monoclonal antibodies will probably be chosen in patients who suffer from chronic or resistant migraines7. Monoclonal antibodies, atogepant, and rimegepant all show comparable efficacy and a possible cost hurdle. Consequently, when choosing from atogepant and monoclonal antibodies, atogepant offers an oral (noninjectable) option for individuals who are unable or unwilling to not self-inject, whereas monoclonal antibodies may permit greater compliance as quarterly or monthly injections7. Given worries about fetal injury in animal experiments, atogepant, like other CGRP medicines, is not advised in individuals who are pregnant or attempting to become pregnant7. Due to its multiple indications in the acute and preventative treatment of migraine, clinicians may prefer the orally administered rimegepant, although it is expensive than atogepant7. Ethical approval None. Sources of funding None. Author contribution All authors contributed in writing the draft, revised and approved the final draft. Conflict of interest disclosures The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) None. Guarantor Abubakar Nazir. Availability of data and materials None.