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Introduction: Rimegepant is an oral small-molecule calcitonin gene-related peptide receptor antagonist approved in several countries for acute treatment of migraine and preventive treatment of episodic migraine in adults. This review summarizes the evidence, published to date, for the use of rimegepant as an acute or preventive treatment of migraine. Areas covered: A brief overview of migraine, the pharmacokinetics of rimegepant, and the mechanism of action of rimegepant are provided. Evidence evaluating rimegepant as an acute or preventive treatment of migraine is then summarized in more detail, based on a literature search for full-length publications related to clinical or real-world use of rimegepant. Expert opinion: Several clinical trials established rimegepant as a safe and effective treatment (acute and preventive) of migraine in adults. There are few head-to-head studies with other migraine treatments to determine relative efficacy. However, the favorable safety profile of rimegepant makes it appropriate for many patients, particularly those with contraindication, intolerance, or inadequate response to other classes of standard-of-care migraine treatments. Additional studies on the efficacy and cost-effectiveness relative to other treatments may further define the role of rimegepant in migraine treatment. [ABSTRACT FROM AUTHOR]

Background: Novel abortive treatments for migraine, ditans and gepants, have promising implications in triptan-insufficient responders with minimal existing comparative data. Our study aims to synthesize evidence through a systematic review and network meta-analysis to assess the comparative efficacy of lasmiditan, rimegepant and ubrogepant in triptan-insufficient responders. Method: We searched PubMed, Embase, CENTRAL, and EBSCO Open Dissertations up to May 2024. We included randomized controlled trials (RCTs) that compared novel abortive treatments, including lasmiditan, rimegepant, and ubrogepant, in migraine patients who self-reported insufficient response to triptans. Outcomes are represented using relative risks with corresponding 95% confidence intervals (CI). The surface under the cumulative ranking curve (SUCRA) was used to rank each medication. Results: A total of five phase 3 RCTs involving 3,004 patients were included in the analysis. All three agents were significantly superior to placebo for two-hour pain freedom (RR = 1.93, 95% CI [1.52, 2.46]), freedom from the most bothersome symptoms at two hours (RR = 1.55, 95% CI [1.37, 1.75]), and pain relief at two hours (RR = 1.46, 95% CI [1.35, 1.58]). No statistically significant differences in efficacy outcomes were observed among the three agents. However, lasmiditan 200 mg had the highest cumulative probability for two-hour pain freedom and relief (SUCRA 0.9, 0.8, respective), while rimegepant led in relieving the most bothersome symptoms (SUCRA 0.7). Conclusion: Lasmiditan, rimegepant, and ubrogepant are effective for acute treatment of migraine in triptan-insufficient responders, with high-dose lasmiditan showing the highest efficacy for pain control. [ABSTRACT FROM AUTHOR]

Objective: To assess tablet utilization patterns and describe pre-treatment characteristics among new users of rimegepant. Background: Rimegepant is the only oral calcitonin gene-related peptide antagonist approved in the United States for both the acute and preventive treatment of migraine. Methods: We conducted a retrospective cohort study of people with migraine who initiated treatment with rimegepant using two US commercial claims databases (MarketScan and Optum). Patients (≥18 years old) with migraine who newly initiated rimegepant were included. Patients were stratified into two groups representing acute (quantity = 8) and prevention (quantity = 15 or 16) use cohorts. Baseline characteristics and medication use history were assessed on index and during the 365-day pre-index period. Rimegepant utilization periods were calculated based on days supplied and varying approaches to define use periods. Tablet quantity per 30 days was reported separately for both acute and prevention cohorts. Results: In MarketScan, a total of 14,037 rimegepant users were identified; 11,195 (79.8%) in the acute group and 1,880 (13.4%) in the prevention group. Rimegepant utilization for acute use was 4.9 ± 2.1 tablets per 30 days and for preventive use was 13.1 ± 7.7 tablets per 30 days. There was high baseline prevalence of triptan contraindications, warnings, and high cardiovascular risk, with a combined 46.2% meeting one or more of these criteria. Acute medication overuse was also common (25.1%) prior to rimegepant initiation. Results were consistent in the Optum database. Conclusion: Our analysis provides the first real-world data available on tablet utilization and characteristics of new users of rimegepant. PLAIN LANGUAGE SUMMARY: There is little information available on the characteristics of people with migraine who start to use rimegepant, which is the only medicine approved for both the prevention of migraine attacks and the acute treatment of migraine attacks after they have started. Information on new users of rimegepant at least 18 years of age was obtained from two commercial databases of US healthcare claims (MarketScan and Optum). The researchers used this information to evaluate people's age, sex, pre-existing illnesses, and prior use of migraine medications at the time they started using rimegepant, and they also used several different methods to estimate how often people used rimegepant after treatment was started. The MarketScan database contained information on 14,037 people with migraine who started using rimegepant, with this group having an average age of 43 years and being comprised mostly of females (88%). Prior to starting rimegepant, almost half (46%) of the people were considered to have high cardiovascular risk and 25% considered at risk of overusing acute migraine medications. Most of the 14,037 people (80%) who started rimegepant used it to treat migraine attacks after they started and this group used approximately 5 tablets every month. The smaller number of people who used rimegepant to prevent migraine attacks used approximately 13 tablets every month. The information obtained from the Optum database was similar to that obtained from the MarketScan database. The researchers' analysis is the first to describe the characteristics of people with migraine who start to use rimegepant outside the setting of a controlled clinical trial. Their results show that new users of rimegepant represent a complex population with a significant profile of pre-existing illness and a diverse treatment history. [ABSTRACT FROM AUTHOR]

Objective: To estimate the number needed to treat and cost per additional responder for atogepant and rimegepant versus placebo for the preventive treatment of episodic migraine (EM) in the United States. Background: Migraine has an enormous impact on a person's daily activities and quality of life, and results in significant clinical and economic burden to both individuals and society. It is important to understand the comparative efficacy and economic value of oral calcitonin gene–related peptide receptor antagonists (gepants) for preventive treatment of EM. Currently, atogepant and rimegepant are US Food and Drug Administration approved for preventive treatment of migraine (rimegepant for EM and atogepant for EM and for chronic migraine). In the absence of head‐to‐head trials, we utilized an indirect treatment comparison on efficacy data from clinical trials conducted for the preventive treatment of EM. We estimated number needed to treat, a valuable metric used in clinical practice to compare treatment efficacy, and cost per additional responder, which can be used to establish the cost effectiveness of a treatment. Methods: An indirect treatment comparison was conducted to compare the efficacy of atogepant 60 mg once daily and rimegepant 75 mg once every other day as preventive treatments for EM using published data from the registrational trials of atogepant (ADVANCE) and rimegepant (BHV3000‐305). The efficacy outcome of interest was ≥50% reduction from baseline in mean monthly migraine/headache days (≥50% responder rate), which was variably defined for a base case and two scenario analyses. Number needed to treat and cost per additional responder versus placebo were calculated and compared between both treatments (weeks 9–12 in the base case analysis; weeks 1–12 and 9–12 for atogepant and during weeks 9–12 for rimegepant in the scenario analyses). Results: In the base case analysis, ≥50% responder rates were 64.9% (95% confidence interval [CI], 53.9–74.5) for atogepant and 51.8% (95% CI, 42.9–60.6) for rimegepant, compared to 44.1% (95% CI, 39.4–49.0) for placebo. The median number needed to treat versus placebo in the base case scenario was 4.8 (95% CI, 3.1–9.0) for atogepant compared to 13.0 (95% CI, 5.9–75.1) for rimegepant. The cost per additional responder versus placebo in the base case scenario was estimated to be $15,823 (95% CI, $11,079–$29,516) for atogepant compared to $73,029 (95% CI, $32,901–$422,104) for rimegepant. Results of the two scenario analyses were consistent with the base case analysis. Conclusions: Atogepant had substantially lower numbers needed to treat and costs per additional responder versus placebo than rimegepant for the preventive treatment of EM across all evaluated scenarios. These analyses suggest that atogepant may be more cost effective than rimegepant for the preventive treatment of EM. Limitations include differences in inclusion/exclusion criteria and in reporting of the ≥50% responder rates between trials. Plain Language Summary: No trials have directly compared atogepant to rimegepant for prevention of episodic migraine, so we used data from published clinical trials to conduct an indirect treatment comparison of these two medicines, estimate the number of patients needed to achieve at least a 50% migraine day reduction, and determine the cost of treatment per additional responder. Our results suggested that 5 patients would need to be treated with atogepant to achieve at least a 50% migraine day reduction, compared to 13 with rimegepant. We also estimated that treatment with rimegepant would cost approximately $60,000 more than treatment with atogepant to achieve a ≥50% reduction in migraine days for one patient. [ABSTRACT FROM AUTHOR]

Introduction: Rimegepant and atogepant, two innovative oral medications for the treatment of migraine, are gaining prominence in the treatment of migraine. However, outside of specialist headache centers, these novel medications remain subjectively underutilized. While multiple rationales exist describing their underutilization, a leading factor is the complexity and clinical flexibility attributed to the individual members of the gepant medication class. Areas Covered: This review provides a brief review of the current uses, common adverse events, and potential areas of future clinical innovation attributed to rimegepant and atogepant. A database search for the term 'Rimegepant OR Atogepant' was completed, yielding 240 individual results. Following multiple rounds of assessment that aimed to determine relevance of each individual result, 42 studies were included in the synthesis of this review. Expert opinion: Rimegepant and atogepant are exciting medications that demonstrate significant clinical innovation within the field of migraine therapy. While current indications are clear, data is lacking regarding the future expanded roles of these medications. Current areas of potential therapeutic innovation for rimegepant and atogepant include the pediatric population, in pregnancy and breastfeeding, in cluster headache and post-traumatic headache, and in patients that previously discontinued calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Novel abortive treatments for migraine, ditans and gepants, have promising implications in triptan-insufficient responders with minimal existing comparative data. Our study aims to synthesize evidence through a systematic review and network meta-analysis to assess the comparative efficacy of lasmiditan, rimegepant and ubrogepant in triptan-insufficient responders. Method We searched PubMed, Embase, CENTRAL, and EBSCO Open Dissertations up to May 2024. We included randomized controlled trials (RCTs) that compared novel abortive treatments, including lasmiditan, rimegepant, and ubrogepant, in migraine patients who self-reported insufficient response to triptans. Outcomes are represented using relative risks with corresponding 95% confidence intervals (CI). The surface under the cumulative ranking curve (SUCRA) was used to rank each medication. Results A total of five phase 3 RCTs involving 3,004 patients were included in the analysis. All three agents were significantly superior to placebo for two-hour pain freedom (RR = 1.93, 95% CI [1.52, 2.46]), freedom from the most bothersome symptoms at two hours (RR = 1.55, 95% CI [1.37, 1.75]), and pain relief at two hours (RR = 1.46, 95% CI [1.35, 1.58]). No statistically significant differences in efficacy outcomes were observed among the three agents. However, lasmiditan 200 mg had the highest cumulative probability for two-hour pain freedom and relief (SUCRA 0.9, 0.8, respective), while rimegepant led in relieving the most bothersome symptoms (SUCRA 0.7). Conclusion Lasmiditan, rimegepant, and ubrogepant are effective for acute treatment of migraine in triptan-insufficient responders, with high-dose lasmiditan showing the highest efficacy for pain control.

Abstract Purpose This study aimed to comprehensively assess the safety of rimegepant administration in real-world clinical settings. Methods Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) spanning the second quarter of 2020 through the first quarter of 2023 were retrospectively analyzed in this pharmacovigilance investigation. This study focuses on employing subgroup analysis to monitor rimegepant drug safety. Descriptive analysis was employed to examine clinical characteristics and concomitant medication of adverse event reports associated with rimegepant, including report season, reporter country, sex, age, weight, dose, and frequency, onset time, et al. Correlation analysis, including techniques such as violin plots, was utilized to explore relationships between clinical characteristics in greater detail. Additionally, four disproportionality analysis methods were applied to assess adverse event signals associated with rimegepant. Results A total of 5,416,969 adverse event reports extracted from the FAERS database, 10, 194 adverse events were identified as the “primary suspect” (PS) drug attributed to rimegepant. Rimegepant-associated adverse events involved 27 System Organ Classes (SOCs), and the significant SOC meeting all four detection criteria was “general disorders and administration site conditions” (SOC: 10018065). Additionally, new significant adverse events were discovered, including “vomiting projectile” (PT: 10047708), “eructation” (PT: 10015137), “motion sickness” (PT: 10027990), “feeling drunk” (PT: 10016330), “reaction to food additive” (PT: 10037977), etc. Descriptive analysis indicated that the majority of reporters were consumers (88.1%), with most reports involving female patients. Significant differences were observed between female and male patients across age categories, and the concomitant use of rimegepant with other medications was complex. Conclusion This study has preliminarily identified potential new adverse events associated with rimegepant, such as those involving the gastrointestinal system, nervous system, and immune system, which warrant further research to determine their exact mechanisms and risk factors. Additionally, significant differences in rimegepant-related adverse events were observed across different age groups and sexes, and the complexity of concomitant medication use should be given special attention in clinical practice.

Abstract Background Rimegepant, a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is indicated for acute and preventive migraine treatment in the United States and other countries. However, there is a lack of prospective real-world evidence for the use of rimegepant in Chinese migraine patients. Methods This was a single-arm, prospective, real-world study. While taking rimegepant to treat migraine attacks as needed, eligible participants were asked to record their pain intensity, functional ability, and accompanying symptoms for a single attack at predose and 0.5, 1, 2, 24, and 48 h postdose via a digital platform. Adverse events (AEs) during the rimegepant treatment period were recorded and analysed. The percentages of participants who experienced moderate to severe pain at predose and 0.5, 1, 2, 24, and 48 h postdose were assessed. Additionally, the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose were analysed. In addition, the total cohort (full population, FP) was stratified into a prior nonresponder (PNR) group to observe the effectiveness and safety of rimegepant for relatively refractory migraine and a rimegepant and eptinezumab (RE) group to observe the effectiveness and safety of the combination of these drugs. Results By November 24th, 2023, 133 participants (FP, n = 133; PNR group, n = 40; RE group, n = 28) were enrolled, and 99 participants (FP, n = 99; PNR group, n = 30; RE group, n = 23) were included in the analysis. Rimegepant was effective in treating migraine in the FP and both subgroups, with a significant decreasing trend in the percentages of participants experiencing moderate to severe pain postdose (p

Abstract Background Orally administered second-generation gepants are effective for the treatment of migraine. The intranasal administration of the third-generation gepant zavegepant might have additional benefits including a rapid onset of action, but it is not clear yet to which extent this has clinical relevance. Methods We examined the effect of zavegepant on the relaxations induced by calcitonin gene-related peptide (CGRP) in human isolated middle meningeal arteries. Furthermore, we connected the pharmacodynamics and pharmacokinetics of gepants by combining data from clinical and basic research. Results We showed that 10 nM zavegepant potently antagonized the functional response to CGRP. We also showed that all gepants are effective at inhibiting functional responses to CGRP at their therapeutic plasma concentrations. Conclusions The relatively low predicted potency of zavegepant to inhibit CGRP-induced relaxation at therapeutic systemic plasma concentrations may point to the relevance of local delivery to the trigeminovascular system through intranasal administration. This approach may have additional benefits for various groups of patients, including overweight patients.

Purpose: This study aimed to comprehensively assess the safety of rimegepant administration in real-world clinical settings. Methods: Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) spanning the second quarter of 2020 through the first quarter of 2023 were retrospectively analyzed in this pharmacovigilance investigation. This study focuses on employing subgroup analysis to monitor rimegepant drug safety. Descriptive analysis was employed to examine clinical characteristics and concomitant medication of adverse event reports associated with rimegepant, including report season, reporter country, sex, age, weight, dose, and frequency, onset time, et al. Correlation analysis, including techniques such as violin plots, was utilized to explore relationships between clinical characteristics in greater detail. Additionally, four disproportionality analysis methods were applied to assess adverse event signals associated with rimegepant. Results: A total of 5,416,969 adverse event reports extracted from the FAERS database, 10, 194 adverse events were identified as the "primary suspect" (PS) drug attributed to rimegepant. Rimegepant-associated adverse events involved 27 System Organ Classes (SOCs), and the significant SOC meeting all four detection criteria was "general disorders and administration site conditions" (SOC: 10018065). Additionally, new significant adverse events were discovered, including "vomiting projectile" (PT: 10047708), "eructation" (PT: 10015137), "motion sickness" (PT: 10027990), "feeling drunk" (PT: 10016330), "reaction to food additive" (PT: 10037977), etc. Descriptive analysis indicated that the majority of reporters were consumers (88.1%), with most reports involving female patients. Significant differences were observed between female and male patients across age categories, and the concomitant use of rimegepant with other medications was complex. Conclusion: This study has preliminarily identified potential new adverse events associated with rimegepant, such as those involving the gastrointestinal system, nervous system, and immune system, which warrant further research to determine their exact mechanisms and risk factors. Additionally, significant differences in rimegepant-related adverse events were observed across different age groups and sexes, and the complexity of concomitant medication use should be given special attention in clinical practice. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions Reported here are the results of four rimegepant phase I studies, in healthy participants, aimed at determining the in vivo potential of rimegepant (75 mg) for cytochrome P450 (CYP) 3A4‐related drug–drug interactions (DDIs).Rimegepant orally disintegrating tablet (Pfizer Inc., New York, NY, USA) is a calcitonin gene‐related peptide receptor antagonist approved for acute treatment of migraine and preventive treatment of episodic migraine. People with migraine commonly use multiple drug treatments, with the potential for DDIs.Each study was an open‐label, single‐arm, single‐sequence, crossover study. Rimegepant was tested as a victim drug by separate co‐administration of itraconazole (a strong CYP3A4 inhibitor and P‐glycoprotein inhibitor) in Study 1, rifampin (a strong CYP3A4 inducer and moderate CYP2C9 inducer) in Study 2, and fluconazole (a strong CYP2C9 inhibitor and moderate CYP3A4 inhibitor) in Study 3, and as a perpetrator drug by co‐administration with midazolam (a CYP3A4 substrate) in Study 4.Mean values of single‐dose rimegepant maximum concentration (Cmax) and area under the curve from time 0 to infinity (AUC0–inf) increased with itraconazole co‐administration (n = 22) by 1.42‐fold (90% confidence interval [CI] 1.25–1.61) and by 4.14‐fold (90% CI 3.87–4.44), respectively, and decreased with rifampin co‐administration (n = 21) to 36% (90% CI 31.2–41.4%) and to 19% (90% CI 16.3–21.4%), respectively. Co‐administration with fluconazole (n = 23) increased rimegepant mean AUC0–inf by 1.80‐fold (90% CI 1.68–1.93), with no impact on Cmax (1.04‐fold; 90% CI 0.94–1.15). Co‐administration of rimegepant single dose (300 mg; n = 14) or multiple doses (150 mg/day; n = 14) increased the mean Cmax of midazolam by 1.38‐fold (90% CI 1.13–1.67) and 1.53‐fold (90% CI 1.32–1.78), respectively, and the AUC0–inf of midazolam by 1.86‐fold (90% CI 1.58–2.19) and 1.91‐fold (90% CI 1.63–2.25), respectively.Based on the magnitude of DDIs, these studies indicate the following: co‐administration of rimegepant with a strong CYP3A4 inhibitor should be avoided; during co‐administration with a moderate CYP3A4 inhibitor, another dose of rimegepant within 48 h should be avoided; co‐administration of rimegepant with a strong or moderate CYP3A4 inducer should be avoided; CYP2C9 does not play a meaningful role in rimegepant metabolism; and there is no clinically meaningful CYP3A4 inhibition by rimegepant. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular (CV) risk factors can limit treatment options for migraine. Rimegepant is an orally administered small-molecule calcitonin gene-related peptide receptor antagonist that does not induce vasoconstriction. The aim of these post hoc subgroup analyses was to assess the safety of rimegepant according to CV risk. Methods: In a multicenter, long-term, open-label, phase II/III safety study, participants with a history of 2–14 migraine attacks per month of moderate or severe pain intensity self-administered rimegepant 75 mg, orally, to treat migraine up to once daily for up to 52 weeks. Uncontrolled, unstable, or recently diagnosed CV disease was part of the exclusion criteria. Safety was assessed across subgroups according to number of CV risk factors (0, 1, or ≥ 2) and Framingham Risk Score (< 10% or ≥ 10%). Results: Of 1800 treated participants, 28.8% had one CV risk factor and 12.1% had ≥ 2 CV risk factors; 7.0% had Framingham Risk Score ≥ 10%. Across the subgroups with 0, 1, and ≥ 2 CV risk factors and Framingham Risk Score < 10% and ≥ 10%, respectively, proportions of participants reporting adverse events (AEs; 59.6%, 61.4%, 62.2%, 59.9%, 67.5%) and serious AEs (2.7%, 2.5%, 2.3%, 2.6%, 2.4%) were consistent, and AEs leading to study drug discontinuation were low (1.9%, 3.1%, 5.5%, 2.5%, 4.8%). Conclusions: Rimegepant showed favorable safety and tolerability in adults with migraine and CV risk factors, including those with moderate to high CV risk. Trial Registration: ClinicalTrials.gov NCT03266588. Plain Language Summary: Older patients with migraine often have cardiovascular (CV) disease – such as a prior heart attack – or risk factors for CV disease. Examples of CV risk factors are high blood pressure, diabetes, smoking, high cholesterol, and a family history of heart disease. The choice of treatments for migraine is limited by safety concerns for patients who have CV risk factors. Newer treatments for migraine – including rimegepant – work differently than older drugs, by targeting calcitonin gene-related peptide. The safety of rimegepant for patients with migraine and CV risk factors can be studied in a clinical trial. In a long-term trial, patients with migraine took rimegepant tablets to treat migraine attacks, up to once a day, for up to 52 weeks. Some of the patients in the study had CV risk factors. We analyzed the results of the study by grouping the patients based on how many CV risk factors they had. We found that the side effects of rimegepant were similar across the groups. This showed that rimegepant was safe and well tolerated in adults with migraine and CV risk factors. [ABSTRACT FROM AUTHOR]

Background: Rimegepant, a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is indicated for acute and preventive migraine treatment in the United States and other countries. However, there is a lack of prospective real-world evidence for the use of rimegepant in Chinese migraine patients. Methods: This was a single-arm, prospective, real-world study. While taking rimegepant to treat migraine attacks as needed, eligible participants were asked to record their pain intensity, functional ability, and accompanying symptoms for a single attack at predose and 0.5, 1, 2, 24, and 48 h postdose via a digital platform. Adverse events (AEs) during the rimegepant treatment period were recorded and analysed. The percentages of participants who experienced moderate to severe pain at predose and 0.5, 1, 2, 24, and 48 h postdose were assessed. Additionally, the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose were analysed. In addition, the total cohort (full population, FP) was stratified into a prior nonresponder (PNR) group to observe the effectiveness and safety of rimegepant for relatively refractory migraine and a rimegepant and eptinezumab (RE) group to observe the effectiveness and safety of the combination of these drugs. Results: By November 24th, 2023, 133 participants (FP, n = 133; PNR group, n = 40; RE group, n = 28) were enrolled, and 99 participants (FP, n = 99; PNR group, n = 30; RE group, n = 23) were included in the analysis. Rimegepant was effective in treating migraine in the FP and both subgroups, with a significant decreasing trend in the percentages of participants experiencing moderate to severe pain postdose (p < 0.05) and a marked increase in the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose compared with predose. AEs were reported by 6% of participants in the FP, and all AEs were mild. Conclusions: In the real world, rimegepant is effective in the acute treatment of migraine patients in China. The low incidence rate of AEs highlighted the favourable tolerability profile of rimegepant. Trial registration: Clinicaltrials.gov NCT05709106. Retrospectively registered on 2023-02-01. [ABSTRACT FROM AUTHOR]

Purpose: This study assesses the cost-effectiveness of rimegepant for the ondemand acute treatment of migraine in the Chinese population, focusing on headache relief within a 2 h timeframe. Utilizing data from Phase III clinical trials on rimegepant involving Asian populations, this analysis aims to provide essential insights for healthcare decision-making in the context of migraine management in China. Patients and methods: Employing a decision tree model, this research evaluates the cost-effectiveness of rimegepant over a concise 2 h period, exclusively considering its direct market price of 219.00 CNY per dose for on-demand, single-use treatment upon approval in China. This model is based on pain relief outcomes from a clinical trial, categorizing health outcomes by the achievement of pain freedom and alleviation from the most bothersome symptom within two hours post-administration. Results: The study unveils that rimegepant adds 0.0018 quality-adjusted life days (QALD) with an incremental cost-effectiveness ratio (ICER) of 122,166.07 CNY/QALD. Against a daily cost-effectiveness threshold derived from the 2023 per capita GDP of China (734.45 CNY/day), rimegepant falls short of proving its cost-effectiveness. A significant price reduction to approximately 1.32 CNY per dose is required for rimegepant to be considered cost-effective within this framework. Furthermore, a series of sensitivity analyses were conducted to validate the robustness of these results. Conclusion: While rimegepant shows clinical efficacy in providing rapid relief from migraine symptoms, its current pricing exceeds the threshold for costeffectiveness in the Chinese healthcare setting. This study underscores the need for price adjustments to enhance the accessibility and economic viability of new migraine treatments. [ABSTRACT FROM AUTHOR]

Background: Orally administered second-generation gepants are effective for the treatment of migraine. The intranasal administration of the third-generation gepant zavegepant might have additional benefits including a rapid onset of action, but it is not clear yet to which extent this has clinical relevance. Methods: We examined the effect of zavegepant on the relaxations induced by calcitonin gene-related peptide (CGRP) in human isolated middle meningeal arteries. Furthermore, we connected the pharmacodynamics and pharmacokinetics of gepants by combining data from clinical and basic research. Results: We showed that 10 nM zavegepant potently antagonized the functional response to CGRP. We also showed that all gepants are effective at inhibiting functional responses to CGRP at their therapeutic plasma concentrations. Conclusions: The relatively low predicted potency of zavegepant to inhibit CGRP-induced relaxation at therapeutic systemic plasma concentrations may point to the relevance of local delivery to the trigeminovascular system through intranasal administration. This approach may have additional benefits for various groups of patients, including overweight patients. [ABSTRACT FROM AUTHOR]

Abstract This commentary addresses the use of rimegepant for situational prevention in migraine management. While the approach of using prophylactic treatments during high-risk periods is not new, its application with rimegepant described by Lipton et al. raises ethical and clinical concerns. These include the challenge of defining high-risk periods, the potential for overmedication, and the risk of medication overuse headache (MOH). The current evidence on MOH with gepants is inconclusive, and recommendations on dosing may be insufficient. Additionally, the long-term safety of calcitonin gene-related peptide (CGRP) antagonists remains uncertain, especially regarding cardiovascular and other systemic effects. The commentary emphasizes the need for caution and thorough investigation into the long-term risks and benefits of situational prevention with rimegepant before widespread adoption.

Abstract Introduction Cardiovascular (CV) risk factors can limit treatment options for migraine. Rimegepant is an orally administered small-molecule calcitonin gene-related peptide receptor antagonist that does not induce vasoconstriction. The aim of these post hoc subgroup analyses was to assess the safety of rimegepant according to CV risk. Methods In a multicenter, long-term, open-label, phase II/III safety study, participants with a history of 2–14 migraine attacks per month of moderate or severe pain intensity self-administered rimegepant 75 mg, orally, to treat migraine up to once daily for up to 52 weeks. Uncontrolled, unstable, or recently diagnosed CV disease was part of the exclusion criteria. Safety was assessed across subgroups according to number of CV risk factors (0, 1, or ≥ 2) and Framingham Risk Score (

Richard B Lipton,1 Alexandra Thiry,2 Beth A Morris,3 Robert Croop3 1Department of Neurology and the Montefiore Headache Center, Albert Einstein College of Medicine, Bronx, NY, USA; 2Biostatistics, Pfizer, Inc., New York, NY, USA; 3Clinical Operations (BM) and Development (RC), Biohaven Pharmaceuticals, Inc., New Haven, CT, USACorrespondence: Richard B Lipton, Montefiore Headache Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Van Etten 3C12, Bronx, NY, 10461, USA, Tel +1 718-430-3896, Email richard.lipton@einsteinmed.eduPurpose: This study compared the efficacy, tolerability, and safety of rimegepant 75 mg oral tablet – a small molecule calcitonin-gene receptor peptide (CGRP) receptor antagonist – with placebo in the acute treatment of migraine.Methods: This double-blind, randomized, placebo-controlled trial enrolled adults aged ≥ 18 years with at least a 1-year history of migraine. Participants randomized to rimegepant 75 mg oral tablet or placebo treated a single migraine attack of moderate or severe pain intensity. The coprimary endpoints, pain freedom and freedom from the most bothersome symptom ([MBS] nausea, photophobia, or phonophobia) at 2 hours postdose, were evaluated using Mantel–Haenszel risk estimation.Results: Of the 1485 participants enrolled, 1162 (78.2%) were randomized to rimegepant (n = 582) or placebo (n = 580). Most participants (85.5%) were female; the population had a mean (SD) age of 41.6 (12.2) years and a history of 4.7 (1.8) migraine attacks per month. At 2 hours postdose, rimegepant-treated participants had higher pain freedom rates (19.2% [104/543] vs 14.2% [77/541]; risk difference 4.9; 95% confidence interval [CI] 0.5 to 9.3; P=0.0298) and MBS freedom rates (36.6% [199/543] vs 27.7% [150/541]; risk difference 8.9; 95% CI 3.4 to 14.4; P=0.0016) than placebo-treated participants. Rimegepant-treated participants also had higher rates of pain relief (56.0% [304/543] vs 45.7% [247/541]; risk difference 10.3; 95% CI 4.4 to 16.2, P=0.0006) at 2 hours postdose. The most common adverse events were nausea (0.9% [5/546] vs 1.1% [6/549]) and dizziness (0.7% [4/546] vs 0.4% [2/549]). No signal of drug-induced liver injury due to rimegepant was identified.Conclusion: Rimegepant 75 mg oral tablet was effective in the acute treatment of migraine. Tolerability and safety were similar to placebo, with no evidence of hepatotoxicity.Trial Registration: Clinicaltrials.gov Identifier: NCT03235479.Plain Language Summary: Researchers wanted to know if rimegepant 75 mg is effective and safe for the acute treatment of migraine. They gave half the participants rimegepant and half placebo and waited 2 hours. Then, they measured the percentages of participants whose headache and most bothersome migraine symptom besides pain (nausea, sensitivity to light or sound) were gone. They also measured side effects to make sure rimegepant is safe.The study included 1084 adults with migraine, 927 (86%) of whom were women. Two hours after taking the medicine: pain freedom was 19% with rimegepant and 14% with placebo. Freedom from the most bothersome symptom was 37% with rimegepant and 28% with placebo. Pain relief rates, defined as the transition from moderate or severe pain to pain that was mild or absent, occurred in 56% with rimegepant and 46% with placebo. The most common side effects were nausea and dizziness, which affected fewer than 1% of rimegepant patients. Rimegepant 75 mg was more effective than placebo for migraine, with similar tolerability and safety.Keywords: migraine, acute, CGRP, rimegepant, efficacy, safety, tablet

Gary Berman,1 Alexandra Thiry,2 Robert Croop3 1Clinical Research Institute, Minneapolis, MN, USA; 2Pfizer Inc., New York, NY, USA; 3Biohaven Pharmaceuticals, New Haven, CT, USACorrespondence: Gary Berman, Clinical Research Institute, 825 Nicollet Mall Suite 1135, Minneapolis, MN, 55402, USA, Tel + 1 612-333-2200, Email gdb@allergy-asthma-docs.comPurpose: To evaluate the safety and tolerability of rimegepant 75 mg for the acute treatment of migraine in participants concurrently using a preventive migraine medication.Patients and Methods: This long-term, open-label safety study (NCT03266588) enrolled adults with a history of 2– 14 moderate or severe migraine attacks per month. Participants self-administered rimegepant 75 mg (1) up to once daily as needed for 52 weeks to treat attacks of any pain intensity or (2) every other day plus as needed for 12 weeks. Preventive migraine medications were allowed if dosing was stable for ≥ 2 months prior to the baseline visit.Results: Of 1800 rimegepant-treated participants, 243 (13.5%) took a concomitant preventive medication. The most common preventive medication was topiramate (26.3%). Rimegepant exposure was comparable in both groups (mean [SD] number of doses per 4 weeks was 7.8 [4.5] in those taking preventives and 7.7 [4.7] in those not taking preventives). The proportion of participants experiencing ≥ 1 on-treatment adverse event (AE) was 68.7% among those using preventive medication and 59.2% among those not using preventives. Serious AEs occurred in 4.5% of those using preventive medication and 2.3% of those who were not using preventives. AEs leading to study drug discontinuation occurred in 4.5% of those taking preventive medication and 2.4% of those not taking preventives. AEs occurring in ≥ 5% of participants in either cohort (with preventives vs without preventives) were upper respiratory tract infection (7.4% vs 9.0%), nasopharyngitis (7.8% vs 6.6%), sinusitis (7.0% vs 4.8%), urinary tract infection (5.3% vs 3.6%), and back pain (5.3% vs 2.8%).Conclusion: Acute treatment of migraine with rimegepant 75 mg for up to 52 weeks was well tolerated and had a favorable safety profile in adults who were concomitantly using preventive migraine medication.Keywords: rimegepant, migraine, preventive, concomitant, safety, clinical trial

Terence Fullerton,1 Glenn Pixton2 1Internal Medicine and Infectious Disease, Pfizer Research and Development, Pfizer Inc., Groton, CT, USA; 2Statistics, Pfizer Inc., Groton, CT, USACorrespondence: Terence Fullerton, Internal Medicine and Infectious Disease, Pfizer Research and Development, Pfizer Inc., 445 Eastern Point Road, Groton, CT, 06355, USA, Tel +1 860-441-6548, Email Terence.Fullerton@pfizer.comPurpose: To examine use of concomitant analgesics and antiemetics during treatment with rimegepant in adults with migraine.Patients and Methods: This was a post hoc analysis of a long-term, open-label, safety study in adults with a history of 2– 14 moderate or severe migraine attacks per month. Participants self-administered rimegepant 75 mg (1) up to once daily as needed (PRN) for 52 weeks or (2) every other day plus PRN (EOD+PRN) for 12 weeks. The PRN cohort was further divided based on baseline attack frequency, with PRN (2– 8) and PRN (9– 14) cohorts having a history of 2– 8 or 9– 14 attacks per month, respectively. Use of select analgesics and antiemetics was analyzed during a 30-day pre-treatment observation period (OP) and during rimegepant treatment.Results: Overall, 1800 rimegepant-treated participants (PRN n = 1514, EOD+PRN n = 286) were included in the analysis. Select analgesics or antiemetics were used by 80.1% of participants during the OP. Among 1441 participants using analgesics or antiemetics during the OP, the proportion who did not use any analgesics or antiemetics following initiation of rimegepant treatment increased during weeks 1– 4 (36.9%), 5– 8 (52.6%), and 9– 12 (56.5%). The mean number of days per month using analgesics or antiemetics was also significantly reduced over time in all cohorts beginning at weeks 1– 4 (P < 0.001 vs OP). This pattern of reduced analgesic or antiemetic use was consistent for all rimegepant cohorts, but was most pronounced in the EOD+PRN cohort in which 74.8% of participants reported ≥ 50% reduction in analgesic/antiemetic days at weeks 9– 12. Reduction in use was maintained over time, with 61.3% of participants not using any analgesics or antiemetics during weeks 49– 52 of PRN treatment.Conclusion: Long-term treatment with oral rimegepant was associated with reduced analgesic and antiemetic use. Clinicaltrials.gov: NCT03266588.Keywords: rimegepant, migraine, analgesics, antiemetics, clinical trial

Rimegepant is a calcitonin gene‐related peptide receptor antagonist approved for migraine treatment. This phase 1, open‐label, single‐center, fixed‐sequence study evaluated the effect of rimegepant on the pharmacokinetics (PK) of metformin. Twenty‐eight healthy participants received metformin 500 mg twice daily from Days 1 to 4 and Days 7 to 10, and once daily on Days 5 and 11. Rimegepant, 75 mg tablet, was administered once daily from Days 9 to 12. At pre‐specified time points, plasma metformin concentration, serum glucose levels, and safety and tolerability were evaluated. A 16% increase in the area under the plasma metformin concentration‐time curve (AUC) for 1 dosing interval (AUC0‐τ,ss), a statistically insignificant increase in maximum and minimum steady‐state metformin concentration (Cmax,ss and Cmin,ss), and a decrease in metformin renal clearance were observed on Day 11 following metformin‐rimegepant coadministration compared with metformin alone; however, the changes were not clinically relevant. Additionally, coadministration of rimegepant with metformin did not induce clinically meaningful change in the maximum observed glucose concentration (Gmax) or AUCgluc compared with metformin alone. Overall, rimegepant and metformin coadministration did not result in clinically relevant changes in metformin PK, renal clearance, or the antihyperglycemic effects of metformin. Rimegepant is considered safe for use with metformin. [ABSTRACT FROM AUTHOR]

Migraine is a chronic condition that manifests itself periodically. It is characterized by recurrent, severe, often hemiplegic, throbbing headaches accompanied by autonomic symptoms in the form of nausea, vomiting, hypersensitivity to noise and light. For many years, triptans have been the gold standard in the treatment of migraine, acting by constricting blood vessels and inhibiting the release of neuropeptides. However, their efficacy is not satisfactory for all patients, especially those with cardiovascular disease. In response to the need for effective and safe therapies, gepants, a new class of drugs that block the calcitonin gene-related peptide (CGRP) receptor, have emerged. Rimegepant, one of the newest representatives of gepant, has been approved for the treatment of migraine both in the acute attack phase and prophylactically. Clinical trials have shown its effectiveness in reducing the number of days with migraine and alleviating associated symptoms. Rimegepant also has a favorable safety profile, making it a promising therapeutic option for migraine patients. This article aims to discuss in detail rimegepant as a new treatment option for migraine, including its mechanism of action, efficacy, safety profile, clinical trial and outlines the benefits of introducing this drug into standard clinical practice.

Introduction and aim of study: Migraine is a chronic neurological disorder that is considered one of the leading causes of disability worldwide. Increasing evidence indicates that the calcitonin gene-related peptide (CGRP), a neuropeptide released during trigeminal nerve activation, plays a major role in pathophysiology and serves as an important therapeutic target. Rimegepant is an antagonist for the receptor of this peptide and an alternative to the commonly used triptans. Materials and Methods: Two databases, Pubmed and Medline, were searched using the terms "rimegepant" and "migraine." Results: By reducing the severity and frequency of migraine attacks, rimegepant significantly improves patients' daily functioning and quality of life. A single 75 mg dose of rimegepant provided better efficacy than placebo in the acute treatment of migraine. Two hours after dosing, significantly more patients in the rimegepant group than in the placebo group reported pain relief (59.3% vs. 43.3%). Rimegepant was also effective in the long term when taken every other day for preventive treatment of migraine and/or as needed for acute migraine treatment. When used, rimegepant was well tolerated in both acute and preventive migraine treatment. The most common adverse events included nasopharyngitis, nausea, urinary tract infection, and upper respiratory tract infection. Conclusions: Rimegepant is an effective drug for treating migraine attacks, offering quick and long-lasting pain relief with a favorable safety profile, especially for patients with contraindications to triptans. Therefore, rimegepant represents a valuable alternative for patients who do not respond adequately to other available migraine therapies.

Abstract Background Rimegepant orally disintegrating tablet (ODT), an oral small-molecule calcitonin gene-related peptide receptor antagonist, is indicated for acute and preventive treatment of migraine in the United States and other countries. Previously, a large clinical trial assessed the efficacy and safety of rimegepant ODT 75 mg for the acute treatment of migraine in adults living in China or South Korea. A post hoc subgroup analysis of this trial was performed to evaluate the efficacy and safety of rimegepant for acute treatment of migraine in adults living in China. Methods Eligible participants were ≥ 18 years of age and had a ≥ 1-year history of migraine, with 2 to 8 attacks of moderate or severe pain intensity per month and

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This commentary addresses the use of rimegepant for situational prevention in migraine management. While the approach of using prophylactic treatments during high-risk periods is not new, its application with rimegepant described by Lipton et al. raises ethical and clinical concerns. These include the challenge of defining high-risk periods, the potential for overmedication, and the risk of medication overuse headache (MOH). The current evidence on MOH with gepants is inconclusive, and recommendations on dosing may be insufficient. Additionally, the long-term safety of calcitonin gene-related peptide (CGRP) antagonists remains uncertain, especially regarding cardiovascular and other systemic effects. The commentary emphasizes the need for caution and thorough investigation into the long-term risks and benefits of situational prevention with rimegepant before widespread adoption. [ABSTRACT FROM AUTHOR]

Background Rimegepant orally disintegrating tablet (ODT), an oral small-molecule calcitonin gene-related peptide receptor antagonist, is indicated for acute and preventive treatment of migraine in the United States and other countries. Previously, a large clinical trial assessed the efficacy and safety of rimegepant ODT 75 mg for the acute treatment of migraine in adults living in China or South Korea. A post hoc subgroup analysis of this trial was performed to evaluate the efficacy and safety of rimegepant for acute treatment of migraine in adults living in China. Methods Eligible participants were ≥ 18 years of age and had a ≥ 1-year history of migraine, with 2 to 8 attacks of moderate or severe pain intensity per month and < 15 headache days per month during the 3 months before screening. Participants self-administered rimegepant ODT 75 mg or matching placebo to treat a single migraine attack of moderate or severe pain intensity. The co-primary endpoints were pain freedom and freedom from the most bothersome symptom (MBS) at 2 h post-dose. Key secondary endpoints included pain relief at 2 h post-dose, ability to function normally at 2 h post-dose, use of rescue medication within 24 h post-dose, and sustained pain freedom from 2 to 24 h and 2 to 48 h post-dose. All p values were nominal. Safety was assessed via treatment-emergent adverse events (TEAEs), electrocardiograms, vital signs, and routine laboratory tests. Results Overall, 1075 participants (rimegepant, n = 538; placebo, n = 537) were included in the subgroup analysis. Rimegepant was more effective than placebo for the co-primary endpoints of pain freedom (18.2% vs. 10.6%, p = 0.0004) and freedom from the MBS (48.0% vs. 31.8%, p <  0.0001), as well as all key secondary endpoints. The incidence of TEAEs was comparable between the rimegepant (15.2%) and placebo (16.4%) groups. No signal of drug-induced liver injury was observed, and no study drug-related serious TEAEs were reported in the rimegepant group. Conclusions A single dose of rimegepant 75 mg rimegepant was effective for the acute treatment of migraine in adults living in China, with safety and tolerability similar to placebo. [ABSTRACT FROM AUTHOR]

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Introduction: There have been no prior trials directly comparing the efficacy of different calcitonin gene-related peptide (CGRP) antagonists for migraine prevention. Reported are the results from the first head-to-head study of two CGRP antagonists, galcanezumab (monoclonal antibody) versus rimegepant (gepant), for the prevention of episodic migraine. Methods: In this 3-month, double-blind, double-dummy study, participants were randomized (1:1) to subcutaneous (SC) galcanezumab 120 mg per month (after a 240 mg loading dose) and a placebo oral disintegrating tablet (ODT) every other day (q.o.d.) or to rimegepant 75 mg ODT q.o.d. and a monthly SC placebo. The primary endpoint was the proportion of participants with a ≥ 50% reduction in migraine headache days per month from baseline across the 3-month double-blind treatment period. Key secondary endpoints were overall mean change from baseline in: migraine headache days per month across 3 months and at month 3, 2, and 1; migraine headache days per month with acute migraine medication use; Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive domain score at month 3; and a ≥ 75% and 100% reduction from baseline in migraine headache days per month across 3 months. Results: Of 580 randomized participants (galcanezumab: 287, rimegepant: 293; mean age: 42 years), 83% were female and 81% Caucasian. Galcanezumab was not superior to rimegepant in achieving a ≥ 50% reduction from baseline in migraine headache days per month (62% versus 61% respectively; P = 0.70). Given the pre-specified multiple testing procedure, key secondary endpoints cannot be considered statistically significant. Overall, treatment-emergent adverse events were reported by 21% of participants, with no significant differences between study intervention groups. Conclusions: Galcanezumab was not superior to rimegepant for the primary endpoint; however, both interventions demonstrated efficacy as preventive treatments in participants with episodic migraine. The efficacy and safety profiles observed in galcanezumab-treated participants were consistent with previous studies. Trial registration: ClinTrials.gov—NCT05127486 (I5Q-MC-CGBD). Plain Language Summary: Galcanezumab and rimegepant are preventive treatments for episodic migraine. The goal of this study was to compare the efficacy of galcanezumab and rimegepant in reducing the number of monthly migraine headaches and to determine if galcanezumab was better than rimegepant. The study provides important information to doctors and their patients when making treatment decisions. People with episodic migraine were assigned to the galcanezumab (given as an injection under the skin) or rimegepant (given as a tablet that dissolves in the mouth) group and treated for 3 months. The doctor and the patient did not know which group they were assigned to, and to keep it unknown to both, people in the galcanezumab group got an injection with real medicine and a fake tablet, and people in the rimegepant group got a tablet with real medicine and a fake injection. The researchers wanted to know how many people in each group had at least a 50% reduction in their monthly migraine headaches. Of the 580 people in the study, 287 were assigned to galcanezumab and 293 to rimegepant. In both groups, most were female and white. After 3 months of treatment, 62% of the people in the galcanezumab group and 61% of people in the rimegepant group had at least a 50% reduction in monthly migraine headaches. Both treatments were effective, but galcanezumab was not better than rimegepant. About 20% of the people in each treatment group had a side effect from the medication, and most were mild or moderate in severity. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy of erenumab versus rimegepant as preventive treatment for patients with episodic and chronic migraine using an anchor-based matching-adjusted indirect comparison. Methods: Patients from two phase II/III trials for erenumab (NCT02066415 and NCT02456740) were pooled and weighted to match on the baseline effect modifiers (age, sex, race, baseline monthly migraine days [MMDs], and history of chronic migraine [CM]) reported in the phase II/III trial for rimegepant (NCT03732638). Four efficacy outcomes were compared between the two erenumab regimens (70 mg and 140 mg) and rimegepant, including changes in MMDs from baseline to month 1 and month 3, changes in Migraine-Specific Quality of Life Questionnaire role function – restrictive domain score from baseline to month 3, and change in disability from baseline to Month 3. Results: Compared with rimegepant, erenumab 70 mg was associated with a statistically significant reduction in MMDs at month 3 (-0.90 [-1.76, -0.03]; p = 0.042) and erenumab 140 mg was associated with statistically significant reductions in MMDs at month 1 (-0.94 [-1.70, -0.19]; p = 0.014) and month 3 (-1.28 [-2.17, -0.40]; p = 0.005). The erenumab regimens also had numerical advantages over rimegepant for other efficacy outcomes. Conclusion: In the present study, we found that erenumab had a more favorable efficacy profile than rimegepant in reducing MMDs at month 1 and month 3 for migraine prevention. These results may help with decision-making in clinical practice and can be further validated in future clinical trials or real-world studies.

Rimegepant is a small‐molecule calcitonin gene‐related peptide receptor antagonist approved for the acute treatment of migraine ± aura and preventive treatment of migraine in adults. The pharmacokinetics of rimegepant in elderly and nonelderly subjects were evaluated. In an open‐label Phase 1 study, 14 elderly (aged 65 years or older) and 14 nonelderly (aged 18 to less than 45 years) subjects each received a single oral dose of rimegepant 75 mg. Blood samples were collected before dosing and through 96 hours after dosing. The pharmacokinetic parameters of rimegepant after a single dose were similar in both age groups. Geometric least‐squares mean ratios (elderly/nonelderly) of the natural log‐transformed maximum observed plasma concentration and natural log‐transformed area under the plasma concentration–time curve from time 0 extrapolated to infinity were 96.6 and 104.6, respectively. Eight (28.6%) subjects (4 elderly, 4 nonelderly) experienced 1 or more adverse events (AEs); all AEs were mild in intensity, and no serious AEs or AEs leading to discontinuation were reported. Following a single 75‐mg dose of oral rimegepant, pharmacokinetic parameters were similar in elderly and nonelderly adults; no dose adjustment is warranted in elderly subjects. [ABSTRACT FROM AUTHOR]

Aims: Migraine is the most common disabling headache disorder and is characterized by recurrent throbbing head pain and symptoms of photophobia, phonophobia, nausea, and vomiting. Rimegepant 75 mg, an oral lyophilisate calcitonin gene-related peptide antagonist, is the first treatment approved for both the acute and preventative treatment of migraine, and the first acute therapy approved in over 20-years. The objective was to assess the cost-utility of rimegepant compared with best supportive care (BSC) in the UK, for the acute treatment of migraine in the adults with inadequate symptom relief after taking at least 2 triptans, or for whom triptans are contraindicated or not tolerated. Materials and methods: A de novo model was developed to estimate incremental costs and quality-adjusted life years (QALYs), structured as a decision tree followed by Markov model. Patients received rimegepant or BSC for a migraine attack and were assessed for response (pain relief at 2-h). Responders and non-responders followed different pain trajectories over 48-h cycles. Non-responders discontinued treatment while responders continued treatment for subsequent attacks, with a proportion discontinuing over time. Data sources included a post-hoc pooled analysis of the phase 3 acute rimegepant trials (NCT03235479, NCT03237845, NCT03461757), and a long-term safety study (NCT03266588). The analysis was conducted from the perspective of the UK National Health Service and Personal Social Services over a 20-year time horizon. Results: Rimegepant resulted in an incremental cost-utility ratio (ICUR) of £10,309 per QALY gained vs BSC, which is cost-effectiveness at a willingness to pay threshold of £30,000/QALY. Rimegepant generated +0.44 incremental QALYs and higher incremental lifetime costs (£4,492). Improved QALYs for rimegepant were a result of less time spent with severe and moderate headache pain. Conclusion: This study highlights the economic value of rimegepant which was found to be cost-effective for the acute treatment of migraine in adults unsuitable for triptans. [ABSTRACT FROM AUTHOR]

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Purpose of Review: Despite the unmet therapeutic needs of patients with chronic migraine (CM) and/or medication overuse, available treatment options are limited. Recently, four calcitonin gene-related peptide receptor antagonists, known as gepants, have been approved for the treatment of migraine. This review focuses on the preventive treatment of CM with gepants and highlights recent findings. Recent Findings: Two randomized controlled trials (RCTs) have shown promising results for rimegepant and atogepant as preventive treatments for CM. In an RCT targeting patients with CM, atogepant demonstrated a significant reduction in the mean monthly migraine days, irrespective of acute medication overuse. Moreover, the patients reported no significant safety concerns and exhibited good tolerance to treatment. Summary: These findings highlight the potential of gepants as a new and effective therapeutic option for patients with CM and/or medication overuse. Gepant use will help improve the management and quality of life of individuals with this debilitating condition. [ABSTRACT FROM AUTHOR]

Purpose of Review: Gepants are small molecules that antagonize calcitonin gene-related peptide (CGRP) receptors. Due to their favorable side effect profile and versatility in treating headaches acutely and preventively, gepants are preferred over triptans. We will cover the indications for the four FDA-approved gepants in adults: rimegepant, atogepant, ubrogepant, and zavegepant. This review will illustrate how gepants will continue to revolutionize the acute and preventive treatment of headaches. Recent Findings: Gepants are now available in oral tablet, dissolving tablet, and intra-nasal spray formulations. Recent studies have shown promising utility in treating the pre-headache or prodromal phase. They have favorable tolerability, no evidence for association with medication overuse, and remain a safer alternative in those who have cerebrovascular risk factors. Additional research is needed to explore occurrence of Raynaud's phenomenon in participants treated with gepants, as it has been associated with CGRP monoclonal antibodies, but are not extensively studied in gepants. Summary: Gepants are expected to play a significant role in the next generation of migraine treatments. [ABSTRACT FROM AUTHOR]

Rimegepant is a small‐molecule calcitonin gene–related peptide receptor antagonist (gepant) with demonstrated efficacy and safety in the acute and preventive treatment of migraine. Here, we report the pharmacokinetics and safety of a single 75‐mg oral dose of rimegepant in subjects with severe, moderate, or mild hepatic impairment and matched healthy subjects from an open‐label, single‐dose, 4‐group phase 1 study. Thirty‐six subjects aged 41‐71 years were enrolled, including 6 each with severe, moderate, or mild hepatic impairment and 18 healthy subjects. All subjects completed the study. A <20% increase in total and unbound pharmacokinetics was observed in subjects with mild hepatic impairment and ≤65% increase with moderate hepatic impairment versus matched healthy controls. Total and unbound systemic exposure increased 2.0‐ and 3.9‐fold in the severe hepatic impairment group. In subjects with severe hepatic impairment, geometric mean ratios (severe impairment/controls) for total concentrations were 202.2% for area under the plasma concentration–time curve from time 0 to the last quantifiable concentration, 202.2% for area under the plasma concentration–time curve from time 0 to infinity, and 189.1% for maximum observed plasma concentration. Corresponding geometric mean ratios using unbound concentrations were 388.8% and 388.7%, respectively. Three (8.3%) subjects reported 4 treatment‐emergent adverse events. Rimegepant is not recommended for use in adults with severe hepatic impairment. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the clinical efficacy and safety of rimegepant for the treatment of migraine in adult patients using a meta-analysis. Methods: The PubMed, EMBASE, and Cochrane Library were searched up to March 2022. Only randomized controlled trials (RCTs) that evaluated migraine and other comparator treatments in adult patients were included. The clinical response at the post-treatment evaluation, including acute pain free and relief effect, whereas the secondary outcomes were the risk of adverse events (AEs). Results: A total of 4 RCTs involving 4,230 patients with episodic migraine were included. Outcome indicators for the number of pain free and relief patients at 2 h, 2-24 h, 2-48 h post-dose showed that rimegepant had better effects relative to the placebo [free at 2 h: OR = 1.84, 95% CI (1.55, 2.18), P < 0.00001; relief at 2 h: OR = 1.80, 95% CI (1.59, 2.04), P < 0.00001]. And there was no significant difference between the occurrence of adverse events in the experimental and control groups [OR = 1.29, 95% CI (0.99, 1.67), P = 0.06]. Conclusion: Rimegepant has better therapeutic effects compared to placebo and no significant difference in adverse events. [ABSTRACT FROM AUTHOR]

Rimegepant is an oral small‐molecule calcitonin gene‐related peptide antagonist for acute migraine treatment with or without aura and prevention of episodic migraine in adults. This was a rimegepant single‐ and multiple‐dose phase 1, randomized, placebo‐controlled, double‐blind study to evaluate the pharmacokinetics and confirm safety in healthy Chinese participants. Participants received a 75‐mg rimegepant orally disintegrating tablet (ODT) (N = 12) or matching placebo (N = 4) ODT on days 1 and 3–7 after fasting for pharmacokinetic assessments. Safety assessments included 12‐lead electrocardiograms, vital signs, clinical laboratory data, and adverse events (AEs). After a single dose (9 females, 7 males) median time to maximum plasma concentration was 1.5 hours; mean values were 937 ng/mL (maximum concentration), 4582 h*ng/mL (area under the concentration–time curve, 0 to infinity), 7.7 hours (terminal elimination half‐life), and 19.9 L/h (apparent clearance). Similar results were seen after 5 daily doses, with minimal accumulation. Six (37.5%) participants experienced ≥1 treatment‐emergent AE: 4 (33.3%) had received rimegepant and 2 (50.0%) had received placebo. All AEs were grade 1 and resolved by the end of the study with no deaths, serious/significant AEs, or AEs leading to discontinuation. Overall, single‐ and multiple‐dose rimegepant ODT 75 mg was safe and well‐tolerated in healthy Chinese adults with similar pharmacokinetics to non‐Asian healthy participants. Trial registration: This trial is registered with the China Center for Drug Evaluation (CDE): CTR20210569 [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of single and multiple doses of rimegepant 75 mg dose on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol (EE)/norgestimate (NGM) in healthy females of childbearing potential or non‐menopausal females with tubal ligation. Background: Females of childbearing age experience the highest prevalence of migraine and frequently inquire about the concomitant use of anti‐migraine medications and contraceptives. Rimegepant, a calcitonin gene–related peptide receptor antagonist, demonstrated efficacy and safety for treating an acute migraine attack and preventing migraine. Methods: This open‐label, single‐center, phase 1, drug–drug interaction study explored the effects of rimegepant 75 mg daily dose on the pharmacokinetics of an oral contraceptive containing EE/NGM 0.035 mg/0.25 mg in healthy females of childbearing potential or non‐menopausal females with tubal ligation. During cycles 1 and 2, participants received EE/NGM once daily for 21 days followed by placebo tablets with inactive ingredients for 7 days. Rimegepant was administered during only cycle 2 for 8 days, from days 12 through 19. The primary endpoint was the effect of single and multiple doses of rimegepant on the pharmacokinetics of EE and norelgestromin (NGMN), an active metabolite of NGM, at steady state, including area under the concentration‐time curve for 1 dosing interval (AUC0−τ,ss) and maximum observed concentration (Css[max]). Results: The study enrolled 25 participants, with pharmacokinetic data assessed for 20 participants. A single 75 mg dose of rimegepant co‐administered with EE/NGM increased exposures of EE and NGMN by ≤16% (geometric mean ratio [GMR], 1.03; 90% confidence interval [CI], 1.01–1.06; and GMR, 1.16; 90% CI, 1.13–1.20, respectively). After 8 days of co‐administering EE/NGM with rimegepant, EE pharmacokinetic parameters, AUC0−τ,ss and Css(max), increased by 20% (GMR, 1.20; 90% CI, 1.16–1.25) and 34% (GMR, 1.34; 90% CI, 1.23–1.46), respectively, and NGMN pharmacokinetic parameters increased by 46% (GMR, 1.46; 90% CI, 1.39–1.52) and 40% (GMR, 1.40; 90% CI, 1.30–1.51), respectively. Conclusions: The study identified modest elevations in overall EE and NGMN exposures after multiple doses of rimegepant, but these elevations are unlikely to be clinically relevant in healthy females with migraine. [ABSTRACT FROM AUTHOR]

Background The acute respiratory syndrome named “COVID-19” is caused by a novel coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Lack of specific antiviral drugs or proper vaccination has led to the development of new therapeutic methods against this virus. Objective The Mpro 3Clpro is the main protease of the SARS-CoV-2 which plays an important role in replication and transcription of the virus. Therefore, targeting this enzyme is a valuable approach for drug development. Methods In the present study, the structural properties of 69 anti-migraine and 212 antiHIV drugs were first obtained from Drug Bank database. To select the appropriate drugs for the enzyme inhibition, the AutoDock Vina software was used. The molecular dynamics (MD) simulation method was applied for better recognition of the structural changes. Results We identified Rimegepant (PubChem ID: 51049968), Dihydroergotamine (PubChem ID: 10531) and Ergotamine (PubChem ID: 8223) as potential inhibitors of Mpro 3Clpro. These complexes were equilibrated after 70 ns. Conclusion Among these compounds, the anti-migraine drug “Rimegepant” showed the highest affinity for binding to the Mpro 3Clpro (-60.8 kJ/mol). This study provides enough evidence for further accomplishment of the identified compounds in the development of effective therapeutics methods against COVID-19.

Migraine headaches are widespread, debilitating and considered a main cause of disability worldwide. Symptoms of migraines include unilateral, pulsating pain that can last for hours to days, frequently associated with photophobia and phonophobia, nausea, or vomiting, and often aggravated by physical activity. The Canadian Headache Society and American Headache Society guidelines suggest strong evidence of the efficacy of triptans, acetaminophen, aspirin, diclofenac sodium, naproxen and ibuprofen for the acute treatment of migraines. The use of calcitonin gene-related peptide (CGRP) antagonists for the treatment and prevention of migraines has been gaining utilization since the approval of the first agent in this class in 2018. There are increasing available options for the acute treatment of migraines. The purpose of this article is to provide a narrative review of the pharmacological and clinical characteristics of ubrogepant and rimegepant and to discuss their implications for use.

Rimegepant is a new drug that has been approved for the acute treatment and prophylactic treatment of migraine in adults. It is the first orally administered CGRP antagonist available in Australia. Studies have shown that rimegepant provides modest benefit compared to placebo for the acute treatment of migraine, with a small difference in pain relief and relief from other symptoms. It has also been found to be superior to placebo for migraine prophylaxis, reducing the number of migraine days per month. Adverse events were generally mild, with nausea and abdominal pain being the most common. Caution is advised when using rimegepant in patients with cardiovascular disease. The drug is metabolized by the CYP3A4 enzyme and should not be used with certain medications. It is classified as category B1 in pregnancy, and while transfer into breastmilk is low, the effects on the infant are unknown. The recommended dose for acute treatment is 75 mg as needed, with a maximum of 75 mg in 24 hours. For prophylaxis, the recommended dose is 75 mg every other day. Rimegepant may serve as an alternative option when other migraine therapies are ineffective or not tolerated, but its role in therapy in Australia is still unclear. [Extracted from the article]

Background: For many years triptans have been the cornerstone of acute migraine treatment. Nevertheless, treatment with triptans may not always be initiated due to contraindications (seen in approximately one fifth of patients) or inadequate response (seen in approximately one third of patients). New acute therapies, including 5-hydroxytryptamine (5-HT)1F receptor agonists, also known as ditans (lasmiditan) and small molecule antagonists of the calcitonin gene-related peptide receptor, also known as gepants (rimegepant and ubrogepant), may be an effective alternative. Methods: We searched Pubmed for keywords, summarized the literature and provided a comprehensive review on the place of next generation acute migraine specific treatments among triptans. Results and conclusion: Post-hoc analyses reported no differences in efficacy of gepants/ditans between responders and non-responders to triptans, but research is hampered by lack of consensus on the definition of non-responder. Due to (partially) overlapping mechanisms of action, it remains unknown whether combination therapy with lasmiditan, gepants and triptans will have added value over monotherapy. Preclinical studies and post-hoc analyses cautiously indicate that these new drugs are safe for patients with cardiovascular risk factors. However, long-term studies are needed to prove cardiovascular safety. The risk of developing medication overuse headache may differ between triptans, ditans and gepants, but further studies are needed to confirm this difference. Head-to-head randomized controlled trials of acute therapies and combinations of therapies are needed to determine their place in migraine treatment among established therapies. [ABSTRACT FROM AUTHOR]

Background: This post-hoc analysis from three phase 3 treatment trials of rimegepant 75 mg — an oral small molecule calcitonin gene-related peptide receptor antagonist for acute and preventive treatment of migraine — assessed efficacy in adults with migraine based on triptan treatment experience. Methods: Participants were assigned to one of four groups based on triptan treatment experience: insufficient response (e.g. lack of efficacy and/or poor tolerability) to 1 triptan, insufficient response to ≥2 triptans, current triptan users, and triptan-naïve participants. The co-primary efficacy endpoints were pain freedom and most bothersome symptom freedom at two hours postdose. Results: In the three trials (N = 3507; rimegepant n = 1749, placebo n = 1758), 1235 (35.2%) participants had a history of insufficient response to 1 triptan (n = 910 [25.9%]) or ≥2 triptans (n = 325 [9.3%]), and 2272 (64.8%) had no history of insufficient response to triptans (current use = 595 [17.0%], naïve = 1677 [47.8%]). Rimegepant was effective on the co-primary endpoints in all subgroups (p ≤ 0.013), except for freedom from the most bothersome symptom in the triptan-naïve group (p = 0.06). No differences on co-primary endpoints were found in pairwise comparisons of rimegepant-treated participants. Conclusions: Rimegepant was effective for the acute treatment of migraine in adults with a history of insufficient response to 1 or ≥2 triptans and in current triptan users. Efficacy on co-primary endpoints did not differ based on the number of insufficient triptan responses. Trial registration: Clinicaltrials.gov: NCT03235479, NCT03237845, NCT03461757 [ABSTRACT FROM AUTHOR]

Introduction: The objectives of this study were to (1) report long-term health-related quality of life (HRQoL) outcomes among patients using rimegepant preventatively in BHV3000-305 (NCT03732638) open-label extension (OLE) and (2) map Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2) to EQ-5D-3L utility values over the double-blind treatment (DBT; 0–12 weeks) and the OLE (13–64 weeks) to assess the influence of treatment on these values. Methods: This was a post hoc analysis using data from a rimegepant study for the prevention of migraine (BHV3000-305). Adult patients with migraine took either rimegepant 75 mg or placebo every other day (EOD) during the DBT phase. All patients received rimegepant during the OLE. MSQv2 was measured at baseline, weeks 12, 24, and 64. A validated algorithm was used to map MSQv2 scores to EQ-5D utilities. Results: Baseline data were available for 347 patients treated with placebo and 348 treated with rimegepant in the DBT period, who continued to the OLE. Baseline EQ-5D utilities were similar between trial arms: 0.598 for placebo and 0.614 for rimegepant. EQ-5D improved from baseline to week 12 and utilities increased by + 0.09 for placebo and + 0.10 for rimegepant (p value = 0.011). By 24 weeks, at which point patients who were originally randomized to placebo had received rimegepant 75 mg EOD for 12 weeks, HRQoL measures (MSQv2 and EQ-5D) were similar across groups, demonstrating rapid onset of treatment effect. This HRQoL improvement was durable out to 64 weeks. Conclusion: Compared to placebo, treatment with rimegepant 75 mg was associated with greater improvement in EQ-5D utilities during the 12-week DBT phase. Patients originally randomized to placebo experienced a similar improvement in EQ-5D utilities after switching to rimegepant during the OLE, demonstrating that benefits are realized within 12 weeks of active treatment. This preventive effect was durable out to 64 weeks and was associated with an additional increase in HRQoL over time. Trial Registration: NCT03732638. [ABSTRACT FROM AUTHOR]