Atogepant 60mg tablets

Migraine, a chronic neurological disorder, imposes a significant burden on individuals and healthcare systems globally. This systematic review and meta-analysis evaluated the efficacy and safety of atogepant in preventing episodic migraine (EM) in adults. A systematic search was conducted in four major databases (PubMed, Scopus, Web of Science, and Cochrane CENTRAL) up to June 2024. The inclusion criteria targeted randomized controlled trials (RCTs) comparing atogepant to placebo or standard care in patients with EM. Statistical analyses were performed using Review Manager (RevMan) software. Four RCTs with 2,018 patients receiving atogepant and 761 patients receiving placebo or standard care were included. Atogepant significantly reduced monthly migraine days compared to placebo at 10 mg daily (mean difference [MD], –1.16 days; 95% confidence interval [95% CI], –1.60 to –0.73), 30 mg daily (MD, –1.15 days; 95% CI, –1.64 to –0.66), 60 mg daily (MD, –1.48 days; 95% CI: –2.36 to –0.61 days), 30 mg twice daily (MD, –1.30 days; 95% CI, –2.17 to –0.43), and 60 mg twice daily (MD, –1.20 days; 95% CI, –1.90 to –0.50). A ≥50% reduction in migraine days was frequently significantly achieved with atogepant across all dosages. Atogepant was generally well tolerated, though it was associated with higher incidence rates of constipation and nausea compared to placebo. Atogepant is an effective and well-tolerated option for preventing EM, offering patients a noninvasive oral alternative to injectable therapies. Further research is warranted to explore its long-term safety and efficacy in diverse patient populations and refine its role in this field.

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BACKGROUND: Atogepant is a CGRP receptor antagonist used in prevention of migraine. This study assesses the safety and efficacy of this drug in management of migraine headaches. METHODS: PubMed, Scopus, Web of Science, and Cochrane CENTRAL were searched until March 24, 2025. Outcomes assessed included monthly migraine and headache day change from baseline at 12 weeks, ≥ 50% reduction in monthly migraine days (MMD), acute medication use days at 12 weeks, treatment-emergent adverse events (TEAE), score on Role Function-Restrictive domain of MSQ at 12 weeks, score on daily activity performance and physical impairment domains of AIM-D at 12 weeks. Subgroup analysis was performed based on different doses of atogepant. RESULTS: Six RCTs comprising of 4052 patients were included. Atogepant showed significant improvement in patients with migraine in terms of MMD over 12 weeks at all doses, 10 mg, 30 mg, and 60 mg. Moreover, it also reduced monthly headache days, had 50% reduction in MMD, and reduced days requiring acute medication use. Atogepant was shown to increase the risk of TEAE, particularly gastrointestinal (GI) side effect including constipation and nausea, however, occurrence of other side effects with atogepant use was insignificant. CONCLUSION: Atogepant is a highly effective CGRP antagonist for migraine prevention, however, it is associated with increased incidence of GI side effects. Further studies are needed to comprehensively investigate the relationship between atogepant dosage and migraine improvement and safety profile.

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Migraine is a complex neurological disorder characterized by recurrent, disabling headaches and various sensory symptoms, affecting about 15% of the global population annually. It is the second most common neurological condition worldwide, causing significant disability. While current prophylactic treatments include beta-blockers, tricyclic antidepressants, anticonvulsants, and monoclonal antibodies targeting the CGRP pathway, not all patients respond adequately. Atogepant, an oral CGRP receptor antagonist, has emerged as a promising option for migraine prevention with improved tolerability. This meta-analysis follows PRISMA guidelines, involving a comprehensive search of Cochrane CENTRAL, PubMed/MEDLINE, and Google Scholar databases up to July 2024. Efficacy outcomes included mean monthly migraine days (MMDs), mean monthly headache days (MHDs), monthly acute medication use days and the percentage of patients with a ≥ 50% reduction in MMDs. Safety outcomes were measured by adverse events (AEs). Statistical analysis employed the Inverse Variance and Mantel-Haenszel random-effects models, with heterogeneity assessed using the I² index. Six RCTs with 4325 patients (3054 on Atogepant, 1271 on placebo) met the inclusion criteria. The combined analysis indicated a significant reduction in MMDs favoring Atogepant over placebo (SMD − 0.39, 95% CI: -0.45 to -0.33; p < 0.00001; I²=0%). Similarly, significant reductions were observed in MHDs, monthly acute medication use days, and the proportion of patients achieving a ≥ 50% reduction in MMDs. Atogepant is an effective and safe option for migraine prophylaxis, showing significant reductions in MMDs. Further extensive trials are recommended to assess the long-term efficacy, safety, and cost efficiency of Atogepant compared to other preventive medications. This systematic review and meta-analysis evaluates the efficacy and safety of Atogepant for migraine prophylaxis based on randomized controlled trials. Atogepant significantly reduces mean monthly migraine days compared to placebo across multiple dosage levels. Significant improvements were observed in monthly headache days, acute medication use, and ≥ 50% responder rates with Atogepant treatment. No significant differences in adverse events were noted between Atogepant and placebo groups, suggesting a favorable safety profile. The meta-analysis highlights Atogepant as an effective and well-tolerated therapeutic option for preventing migraines, warranting further research on long-term outcomes.

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BACKGROUND AND OBJECTIVES: Atogepant is an oral, calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine. We evaluated the efficacy of atogepant for the preventive treatment of chronic migraine (CM) in participants with and without acute medication overuse. METHODS: This subgroup analysis of the phase 3, 12-week, randomized, double-blind, placebo-controlled PROGRESS trial evaluated adults with a ≥1-year history of CM, ≥15 monthly headache days (MHDs), and ≥8 monthly migraine days (MMDs) during the 4-week baseline period. Participants were randomized (1:1:1) to placebo, atogepant 30 mg twice daily (BID), or atogepant 60 mg once daily (QD) for 12 weeks and were analyzed by acute medication overuse status (triptans/ergots for ≥10 days per month, simple analgesics for ≥15 days per month, or combinations of triptans/ergots/simple analgesics for ≥10 days per month). Outcomes included change from baseline in mean MMDs, MHDs, and monthly acute medication use days; ≥50% reduction in mean MMDs across 12 weeks; and patient-reported outcome (PRO) measures. RESULTS: Of 755 participants in the modified intent-to-treat population, 500 (66.2%) met baseline acute medication overuse criteria (placebo, n = 169 [68.7%]; atogepant 30 mg BID, n = 161 [63.6%]; atogepant 60 mg QD, n = 170 [66.4%]). The least squares mean difference (LSMD) (95% CI) from placebo in MMDs was -2.7 (-4.0 to -1.4) with atogepant 30 mg BID and -1.9 (-3.2 to -0.6) with atogepant 60 mg QD. Mean MHDs (LSMD [95% CI] -2.8 [-4.0 to -1.5] and -2.1 [-3.3 to -0.8]) and mean acute medication use days (LSMD [95% CI] -2.8 [-4.1 to -1.6] and -2.6 [-3.9 to -1.3]) were reduced and a higher proportion of participants achieved ≥50% reduction in MMDs (odds ratio [95% CI] 2.5 [1.5-4.0] and 2.3 [1.4-3.7]) with atogepant 30 mg BID and atogepant 60 mg QD. There was a 52.1%-61.9% reduction in the proportion of atogepant-treated participants meeting acute medication overuse criteria over 12 weeks. Atogepant improved PRO measures. Similar results were observed in the subgroup without acute medication overuse. DISCUSSION: Atogepant was effective in participants with CM, with and without acute medication overuse, as evidenced by reductions in mean MMDs, MHDs, and acute medication use days; reductions in the proportion of participants meeting acute medication overuse criteria; and improvements in PROs. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT03855137. Submitted: February 25, 2019; first patient enrolled: March 11, 2019. clinicaltrials.gov/ct2/show/NCT03855137. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that atogepant reduces mean MMDs, MHDs, and monthly acute medication use days in adult patients with or without medication overuse.

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BACKGROUND: Atogepant, the first oral CGRP receptor antagonist approved for migraine prevention, has demonstrated efficacy and safety in randomized clinical trials (RCT). However, prospective real-world data are lacking. OBJECTIVE: To explore the effectiveness, safety, and tolerability of atogepant 60 mg at week 12 in patients with high-frequency episodic (HFEM: 8-14 days/month) or chronic migraine (CM) with multiple therapeutic failures. METHODS: This ongoing, multicenter (n = 16), prospective real-world study included consecutive adults with HFEM or CM who had failed ≥3 prior preventive treatments, according to AIFA criteria. Participants received atogepant 60 mg daily, with treatment planned for up to 12 months. PRIMARY ENDPOINT: change from baseline to week 12 in monthly migraine days (MMD) for HFEM and monthly headache days (MHD) for CM. Secondary endpoints: changes in monthly analgesic intake (MAI), pain intensity (NRS), disability (HIT-6, MIDAS), interictal burden (MIBS-4), treatment satisfaction (PGIC), responder rates (≥ 50%, ≥ 75%, 100%), and changes in migraine frequency during the first treatment week compared to the last pre-treatment week. Adverse events were monitored throughout. RESULTS: A total of 183 patients were enrolled and 82 completed ≥ 12 weeks of follow-up. Of these, 41.5% had previously failed anti-CGRP mAbs. At week 12, significant reductions (p < 0.001) were observed in MMD (-6.0) and MHD (-11.2). Secondary outcomes also improved significantly (p < 0.001): MAI (-10.9), NRS (-2.7), HIT-6 (-13.2), MIDAS (-61.1), and MIBS-4 (-5.4). Responder rates were 65.9% (≥ 50%), 36.6% (≥ 75%), and 6.1% (100%). PGIC documented high satisfaction (much/very much improved: 70.7%). A significant decrease (p < 0.001) in migraine frequency was already evident by week 1 (overall: - 2.5 days, HFEM: - 1.5, CM: - 3.1). In the mAb-failure subgroup, ≥ 50% and ≥ 75% response rates were 52.9% and 23.5%, with significant improvements in all primary and secondary endpoints (p < 0.001). Adverse events occurred in 5.5% of patients, and 1.6% discontinued treatment. CONCLUSION: The GIANT study provides real-world evidence of atogepant's effectiveness, safety, and tolerability in patients with HFEM and CM with multiple therapeutic failures and comorbidities. It extends RCT data by showing rapid onset of action, meaningful reductions in pain intensity and interictal disability, high patient satisfaction, and effectiveness even in patients with anti-CGRP mAb failures.

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Background Focusing on calcitonin gene-related peptide (CGRP) as a specific target has changed and improved migraine management. After the positive results of monoclonal antibodies directed to the CGRP pathway (anti-CGRP mAbs), randomized controlled trials also demonstrated the efficacy of gepants in migraine prevention. The present study aimed to assess the effectiveness of atogepant in preventing migraine after a 12-week treatment in clinical practice. Methods Adult patients with a clinical indication for atogepant 60 mg daily were screened for participation in this multicentric prospective observational cohort study. At baseline (T0) and after 12 weeks (T3) since the first atogepant administration, monthly migraine days (MMDs), monthly headache days (MHDs) and monthly acute medications (MAMs) were assessed. The co-primary endpoints were the changes in MMDs from T0 to T3 and the percentage of T3 Responders (those with a reduction of MMDs ≥50%, i.e. 50% response rate (RR)). At T0 and T3, we also collected the Headache Impact Test (HIT-6), the Migraine Disability Assessment (MIDAS) questionnaire, the Migraine Treatment Optimization Questionnaire-6 (mTOQ-6), the Migraine-Specific Quality-of-Life Questionnaire (MSQ), the 12-item Allodynia Symptom Checklist (ASC-12) and the Migraine Interictal Burden Scale (MIBS-4). Results One hundred and six patients (56/106 (52.8%) with chronic migraine (CM), 93/106 (87.7%) female, aged 50.6 ± 13.2 years) from 10 Italian centers completed the 12-week observation since the first atogepant tablet intake. From baseline to T3, a reduction of 6.9 MMDs (SD 9.7; p &lt; 0.001) was achieved in the whole group and, specifically, of −4.9 (SD 6.6; p &lt; 0.001) in episodic migraine (EM) and of −8.6 (SD 11.7; p &lt; 0.001) in CM patients. Overall, 60/106 (56.6%) of patients were Responders (60.0% in the EM and 46.4% in the CM group). Non-Responders previously experienced more ineffective treatments than Responders with anti-CGRP mAbs (65.2% vs. 43.3%, respectively, p = 0.031) and with onabotulinumtoxinA (56.5% vs. 28.3%, p = 0.005), and presented more medication overuse at baseline (55.7% vs. 44.3%, p = 0.003). However, no baseline characteristics were significantly associated with the Responder status in the multiple regression analysis. For T0 to T3, MAMs, MIDAS, ASC-12 and mTOQ-6 reduced ( p ≤ 0.001 consistently), and MSQ role-function restriction increased ( p = 0.026), whereas HIT-6 and MIBS-4 did not change. Only seven subjects (7/106, 6.6%) dropped out of atogepant treatment: four for lack of effectiveness and three for adverse events or poor tolerability. Conclusions The STAR study demonstrates the effectiveness and tolerability of atogepant 60 mg at 12 weeks in a real-world setting. Previous ineffective anti-CGRP mAbs were not a relevant prognostic factor. Trial Registration The study was preregistered on clinicaltrial.gov, NCT06414044.

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BACKGROUND: Published evidence supporting efficacy of calcitonin gene-related peptide receptor antagonists as acute migraine treatments in males is limited. METHODS: To fill the gap, we present male and female data from four ubrogepant and four atogepant randomized, double-blind, placebo-controlled trials for acute and preventive treatment of migraine, respectively. Acute outcomes included 2-h pain freedom and absence of most bothersome symptom (co-primary; headache-phase randomized, double-blind, placebo-controlled trials); absence of moderate-to-severe headache within 24 h (primary; prodrome randomized, double-blind, placebo-controlled trial). Preventive outcome included change from baseline in mean monthly migraine days across 12 weeks (primary). RESULTS: Pooled data from phase 3 headache-phase ubrogepant randomized, double-blind, placebo-controlled trials showed similar rates of pain freedom (19.4% vs 21.1%) and absence of most bothersome symptom (35.1% vs 39.0%) 2 h post-dose between males and females, respectively. Time course of pain freedom and absence of most bothersome symptom over 48 h was similar between male and female subgroups. Comparable reductions in mean monthly migraine days across 12-week treatment periods were found between males and females treated with atogepant 60 mg once-daily in pooled episodic migraine and chronic migraine randomized, double-blind, placebo-controlled trials. CONCLUSION/INTERPRETATION: In ubrogepant and atogepant randomized, double-blind, placebo-controlled trials, although analysis power for males is limited due to small sample sizes, evidence supports similar treatment effects in males and females with migraine. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02828020; NCT02867709; NCT04492020; NCT01613248; NCT02848326; NCT03777059; NCT04740827; NCT03855137.

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Background The discovery of calcitonin gene-related peptide (CGRP) as a key player in migraine pathophysiology has revolutionized the approach to preventive treatment. Atogepant, an oral small-molecule CGRP receptor antagonist, has shown promising efficacy in randomized controlled trials (RCTs) for both episodic and chronic migraine. However, real-world evidence, particularly in individuals with chronic migraine and multiple preventive treatment failures, remains limited. This study is aimed to evaluate the effectiveness, safety, and tolerability of daily atogepant 60 mg in a homogeneous cohort of resistant individuals with chronic migraine over a 24-week period to extend the short-term observation assessed in previous real-world studies. Methods In the present real-world, prospective, monocentric study, a total of 100 participants (93% female; mean ± SD, age 43 ± 11 years) with chronic migraine with at least three previous treatment failures without medication overuse headache were consecutively recruited and received atogepant 60 mg daily for six months. All participants had failed a median of six previous preventive treatments, including CGRP-monoclonal antibodies (mAbs) (68%) and onabotulinumtoxin-A (BoNT-A) (14%). Primary outcomes included change in monthly migraine days (MMDs) and greater than 50% responder rate at 12 and 24 weeks. Secondary outcomes included changes in monthly headache days (MHDs), acute medication intake (MAMI), headache impact (Headache Impact Test (HIT-6)), anxiety and depression (Hospital Anxiety and Depression Scale (HADS)) and patient satisfaction (Patient's Global Impression of Change (PGIC)), change in MMDs, demographic and clinical features associated with greater than 50% responder rate, as well as effectiveness in individuals with previous CGRP-mAbs failure. Treatment-emergent adverse events (TEAEs) were also recorded. Results At weeks 12 and 24, MMDs were reduced by 5.6 and 7.1 days from baseline, respectively ( p &lt; 0.001), while 45% and 53% of participants achieved a ≥ 50% reduction in MMDs. Significant improvements were also seen in MHDs (−8.1 days), MAMI (−5.1 days) and HIT-6 scores (−6.2 points). Conversion from chronic to episodic migraine occurred in 60% of participants. PGIC results showed that 69% of participants reported feeling “much” or “very much” better. Logistic regression identified higher socioeconomic status (odds ratio = 2.87) as a positive predictor and previous CGRP-mAb failure (odds ratio = 0.38) as a negative predictor of treatment response. Nevertheless, among individuals with more than one CGRP-mAb failure, 47% achieved a ≥50% reduction in MMDs. TEAEs were reported by 53% of participants, with constipation (28%) and fatigue (16%) being the most common. Conclusions Atogepant 60 mg daily demonstrated meaningful clinical benefit and good tolerability in real-world individuals with treatment-resistant chronic migraine over a 24-week period. These findings extend data from RCTs and real-world studies limited to 12-week period of observation, supporting atogepant as an effective option even in individuals with prior CGRP-mAb failure.

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Background Atogepant is an oral calcitonin gene–related peptide receptor antagonist approved in the US and EU for the preventive treatment of migraine in adults. We evaluated the efficacy, safety, and tolerability of atogepant for the preventive treatment of episodic migraine (EM) in Japanese participants. Methods RELEASE was a phase 2/3, multicenter, randomized, double-blind, placebo-controlled study enrolling adult participants with a ≥1-year history of migraine, &lt;50 years of age at time of migraine onset, history of 4–14 monthly migraine days (MMDs), and &lt;15 monthly headache days in the three months prior to screening and during the screening/baseline period. The study included a four-week screening/baseline period, 12-week double-blind treatment period (DBTP), 12-week active treatment extension period, and 30-day safety follow-up. Participants were randomized 1:1:1:1 to placebo, atogepant 10 mg once daily (QD), 30 mg QD, or 60 mg QD for the 12-week DBTP. Completers of the DBTP could continue to the 12-week active treatment extension period where the placebo group was rerandomized 1:1:1 to atogepant 10 mg, 30 mg, or 60 mg; atogepant groups continued the same dose. The primary endpoint was the change from baseline in mean MMDs across the 12-week DBTP. Results Of 807 participants screened, 523 were treated in the 12-week DBTP (Safety Population 1 [placebo, N = 134; atogepant 10 mg, N = 126; 30 mg, N = 131; 60 mg, N = 132]; modified intent-to-treat population [placebo, N = 133; atogepant 10 mg, N = 127; 30 mg, N = 130; 60 mg, N = 131]). The least square mean difference (95% confidence interval) from placebo in mean MMDs across 12 weeks was −1.57 (−2.24, −0.89) for atogepant 10 mg, −1.90 (−2.57, −1.22) for 30 mg, and −2.10 (−2.78, −1.43) for 60 mg (all p &lt; 0.0001). Treatment-emergent adverse events (TEAEs) in the DBTP occurred in 46.3%, 45.2%, 38.9%, and 43.2% of participants receiving placebo, atogepant 10 mg, 30 mg and 60 mg, respectively. During the DBTP, TEAEs occurring ≥5% were constipation and nasopharyngitis, and there was one serious TEAE in the atogepant 10 mg group considered not related to treatment. TEAEs resulting in treatment discontinuation were infrequent in all treatment groups in the DBTP. Safety was consistent in the 12-week active treatment extension period. Conclusions Atogepant treatment demonstrated statistically significant and clinically meaningful reductions in mean MMDs compared with placebo across the 12-week DBTP in Japanese participants with EM. The safety profile of atogepant in Japanese participants was consistent with the known safety profile in the global population. No new safety signals were identified. Trial registration ClinicalTrials.gov NCT05861427; https://clinicaltrials.gov/study/NCT05861427

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