Qulipta (atogepant) / Merck (MSD), AbbVie - LARVOL DELTA

Gepants: targeting the CGRP pathway for migraine relief. (PubMed, Front Pharmacol) - "Several new agents (atogepant, ubrogepant, rimegepant, and zavegepant) expand therapeutic options beyond traditional triptans and monoclonal antibodies. Gepants represent a valuable advancement in migraine therapy, offering effective acute and preventive options with favorable tolerability, particularly for patients who cannot use triptans or who have cardiovascular risk factors. Ongoing studies will clarify long-term safety, real-world effectiveness, and potential roles in combination or sequential therapy."

Journal • Review • Cardiovascular • CNS Disorders • Fatigue • Migraine • Pain

AbbVie to Present Phase 3 ECLIPSE Data Demonstrating Atogepant (AQUIPTA) Superiority Over Placebo in Achieving Pain Freedom for the Acute Treatment of Migraine at the 19th European Headache Congress (WVNews) - "The Phase 3 ECLIPSE study demonstrated that atogepant was superior to placebo in achieving pain freedom at two hours after treatment of the first migraine attack in adults with a history of migraine (with or without aura) (24.3% for atogepant vs. 13.1% for placebo; odds ratio 2.36, 95% CI [1.76, 3.15]; p<0.0001). Additionally, the first 12 of the 16 key secondary endpoints met statistical significance, including freedom from MBS at 2 hours after treatment (p<0.0001)."

P3 data • Migraine

Combination preventive therapy with onabotulinumtoxinA and atogepant for chronic migraine: A 24-week, prospective, real-world evaluation (SYNERGY study). (PubMed, Cephalalgia) - "Adverse events were mild and consistent with known safety profiles for both drugs separately; no novel safety concerns emerged.ConclusionsThe addition of atogepant to BoNTA might be effective and well tolerated in real-world setting, including CM patients previously exposed to multiple preventives. Prospective controlled trials and health-economic evaluations are warranted to validate these observations and inform future clinical guidelines."

HEOR • Journal • Real-world evidence • CNS Disorders • Migraine • Pain

Predictive factors of response to anti-CGRP monoclonal antibodies in patients with multiple sclerosis (EHF-EHC 2025) - "Mainly used DMTs were ocrelizumab (25.5%), natalizumab (19.1%), and dimethyl fumarate (17.0%), while anti-CGRP treatments included anti-CGRP mAbs (95%) and atogepant (5%)...We confirm the safety of combined DMT and CGRP treatments in patients with both conditions. Timely and tailored therapy should be planned early in MS disease course to achieve the best outcomes."

Biomarker • Clinical • CNS Disorders • Migraine • Multiple Sclerosis

MIGRA-MS: A case series on chronic migraine and multiple sclerosis (EHF-EHC 2025) - "Prior treatments included interferons and glatiramer acetate; current therapies consisted of ocrelizumab, natalizumab, alemtuzumab, teriflunomide, or dimethyl fumarate...All received a median of three classic preventives (amitriptyline in all cases) and onabotulinumtoxinA (PREEMPT, 155 IU) with only one responder; two patients received an extended dose (195 IU) without benefit and later CGRP monoclonal antibodies (galcanezumab, erenumab, eptinezumab) with no response, and atogepant with only transient or partial benefit...In this case series of relapsing–remitting MS with chronic resistant migraine, response to onabotulinumtoxinA and anti-CGRP therapies was limited, with no drug interactions or adverse effects observed. An individualized approach and further studies are needed to assess emerging treatments in this subgroup."

Clinical • CNS Disorders • Migraine • Multiple Sclerosis • Pain

Efficacy and tolerability of atogepant during the perimenstrual phase of female cycle (EHF-EHC 2025) - "The treatment was well tolerated in this cohort. Ongoing data collection will further clarify the impact of hormonal fluctuations on treatment response throughout the menstrual cycle."

Clinical • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Migraine

Migraine worsening after excellent initial response to galcanezumab (EHF-EHC 2025) - "Several prophylactics were tried (topiramate, amitriptyline, and atogepant) with no improvement...However, in the last few months of treatment, she experienced recrudescence of symptoms – she's now awaiting treatment with eptinezumab...While he tried several preventive medications (topiramate, amitriptyline, venlafaxine and valproic acid), he was also medicated with corticosteroids...Recent literature and medical experience refer to Galcanezumab as a good sustained treatment to refractory migraine. However, these cases highlight the situations in which, despite the initial response being great, there's no prolonged effect on pain relief."

Cardiovascular • CNS Disorders • Complement-mediated Rare Disorders • Hepatology • Hereditary Angioedema • Migraine • Pain

Efficacy, safety, and tolerability of atogepant in migraine patients from the UAE (EHF-EHC 2025) - "Ten patients who reported AEs continued treatment, while two discontinued at the 6th (constipation and fatigue) and the 9th (constipation and nausea) visits due to the side effects. Atogepant effectively reduced monthly migraine days in both chronic and episodic migraine patients and was generally safe and well-tolerated among patients in the UAE."

Clinical • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Migraine • Pain

Mid-term effectiveness and tolerability of atogepant in the prevention of migraine: A real life, prospective, multicentric study (the STAR study) (EHF-EHC 2025) - "Weight reduced of 0.8±3.1 kg (p <0.001) from T0 to T3, while from T3 to T6 remained stable. The multicentric STAR study confirms atogepant effectiveness and tolerability at 24-week follow-up."

Clinical • CNS Disorders • Migraine • Pain

Refractory chronic cluster headache: A new therapeutic option (EHF-EHC 2025) - "Acute therapy with oral zolmitriptan 5 mg, subcutaneous sumatriptan 6 mg, and oxygen were used, with moderate effect. Preventive treatment included prednisolone and occipital nerve block during exacerbations, and verapamil, both as monotherapy and in combination with topiramate and lithium in various regimens...Treating refractory chronic cluster headache is challenging, as it is highly disabling for the patient. Although other therapies targeting CGRP have not shown clear benefit in clinical trials, especially in chronic forms, atogepant may offer a promising alternative."

Anorexia • Cardiovascular • Chronic Cluster Headache • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Hypertension • Migraine • Pain

Use of gepants in the acute treatment and bout modulation of cluster headache: A retrospective case series (EHF-EHC 2025) - "Notably, no traditional preventive therapies (e.g., verapamil, corticosteroids) were used during the reported bout Retrospective case series of six CH patients who used gepants during a recent cluster bout...Rimegepant 70 mg (every other day, 16–28 days) was used by four patients; two used atogepant 60 mg/day (28 days)...Their efficacy in chronic CH remains uncertain. These preliminary findings warrant confirmation in prospective, controlled studies"

Retrospective data • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Migraine • Pain

Four‑year real‑world efficacy and tolerability of anti‑CGRP therapies in a tertiary headache centre in England (EHF-EHC 2025) - "A total of 548 treatments were initiated in 415 patients (rimegepant: n=57; atogepant: n=60; erenumab: n=283; fremanezumab: n=136; galcanezumab: n=12). Atogepant was associated with the most adverse effects, with constipation, dizziness, and "brain fog" reported. Fremanezumab was associated with a higher treatment success rate than erenumab, rimegepant, and atogepant in our cohort."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Migraine • Pain

Satisfaction rates and self-reported adverse events of antiCGRP therapies for migraine prevention – Focus on patient perspectives (EHF-EHC 2025) - "4% of questionnaires corresponded to patients on Atogepant, 9.3% on Erenumab , 24.4% on Eptinezumab, 29% on Galcanezumab and 32% on Fremanezumab. Most frequent, were gastrointestinal symptoms and local skin reactions. Nevertheless, some other complaints were not expected such as weight gain, dizziness, palpitations and chest pain arising in more than 10% of patients, showing the need for maintaning recent therapies adverse events surveillance"

Adverse events • Clinical • Cardiovascular • CNS Disorders • Hypertension • Migraine • Pain

Adverse effects and predictors of their occurrence in a series of patients with resistant migraine treated with atogepant (EHF-EHC 2025) - "In our cohort, higher body weight was associated with a greater incidence of adverse effects related to Atogepant. Further studies are needed to confirm these data and determine whether this association is related to the absorption, transport, or metabolism of this drug."

Adverse events • Clinical • CNS Disorders • Constipation • Dermatology • Gastroenterology • Gastrointestinal Disorder • Migraine • Pain • Pruritus • Sleep Disorder

The efficacy of gepants in the prophylactic management of migraine: A systematic review (EHF-EHC 2025) - "PubMed and BVS were searched through March 2025 for randomized controlled trials (RCTs) evaluating rimegepant or atogepant for migraine prevention. Their favorable safety profile and ease of use make them a valuable alternative to existing therapies. Further long-term, head-to-head studies are needed to confirm their sustained efficacy and comparative effectiveness."

Clinical • Review • CNS Disorders • Migraine • Pain

Treatment switching after first Anti-CGRP MAb failure in migraine: Gepants or another MAb? (EHF-EHC 2025) - "This retrospective observational study included patients from a tertiary Headache Unit who switched to a gepant (atogepant or rimegepant) or to a second mAb following the failure of a first mAb between May 2024 and March 2025. Switching to a gepant or another mAb after failure of a first mAb shows similar overall outcomes. However, a trend towards a higher clinical response and better tolerability was observed in the gepant group, warranting further confirmation in prospective comparative studies."

CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Migraine • Pain

Response and super-response to atogepant high-frequency episodic and chronic migraine at 24-week: Results from the GIANT II Study (EHF-EHC 2025) - "Notably, most prior anti-CGRP mAb non-responders benefited (~71% responders; ~40% super-responders). The treatment was well tolerated and safe."

CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Migraine • Pain

Local cutaneous complications of CGRP monoclonal antibodies: A case series (EHF-EHC 2025) - "Nine women treated with subcutaneous anti-CGRP monoclonal antibodies developed mild/moderate local cutaneous reactions (mainly erythema, induration, edema, and pruritus) representing 5% of all treated patients (n=190; fremanezumab 88, galcanezumab 75, erenumab 27)...Two continued therapy with supportive measures (local cooling, topical corticosteroid cream, pre/post-injection antihistamines, and rotation of injection site to abdominal area), while five required switching due to persistent reactions with or without lack of efficacy: two to atogepant, one to erenumab then eptinezumab, and one directly to eptinezumab; one discontinued...Supportive measures allowed continuation in some cases, but most required switching to another monoclonal antibody or a gepant. Monitoring and proactive management are essential to minimize treatment discontinuation."

Clinical • CNS Disorders • Dermatology • Immunology • Migraine • Pruritus

Neurophysiological effects of atogepant in episodic migraine: The ATOM project (EHF-EHC 2025) - "PEV evaluation showed a lack of habituation both at T0 and T1 (habituation index: T0: 92.2 ± 22.1 vs. T1 93.2 ± 13.1, p=0.794). Our findings suggest that after a 3-month atogepant treatment there is an improvement in central sensitization mechanisms and a modulation of the habituation pattern."

CNS Disorders • Migraine • Pain

A prospective real-world analysis of atogepant in refractory migraine patients (EHF-EHC 2025) - "The most common were constipation (19%), decreased appetite/weight loss (13%), nausea/vomiting (12%), fatigue (12%), and dizziness (5%), all considered mild Atogepant appears to be an effective and well-tolerated treatment for patients who are refractory to other preventive therapies, including those who failed to respond or tolerate previously a CGRP mAbs. These real-world findings support atogepant"s utility in complex clinical populations."

Clinical • Real-world • Real-world evidence • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Migraine • Pain

Efficacy, safety, and tolerability of atogepant for the acute treatment of migraine: Results from the ECLIPSE trial (EHF-EHC 2025) - "No new safety signals were identified. Atogepant was efficacious, safe, and well tolerated for the acute treatment of migraine."

Clinical • CNS Disorders • Migraine • Pain

Risk of hypertension with Atogepant use in migraine patients in the UAE (EHF-EHC 2025) - "Paired t-tests showed no statistically significant differences in systolic or diastolic blood pressure at any follow-up visit (p > 0.05). Atogepant use in migraine patients was not associated with any significant changes in systolic or diastolic blood pressure, indicating no apparent risk of hypertension in this population."

Clinical • Cardiovascular • CNS Disorders • Hypertension • Migraine • Pain

Safety, tolerability and efficacy of atogepant added to onabotulinumtoxina for the preventive treatment of chronic migraine: A phase 3, multicenter, 24-week, open-label study (EHF-EHC 2025) - P3 | "Combination management with onabotA and atogepant for CM appears to be safe and generally well-tolerated. In this study the addition of atogepant to onabotA resulted in clinically meaningful reductions in migraine days and improvement in responder rates, reflecting the potential benefit of utilizing combination therapy with distinct but complementary mechanisms of action for CM management."

Clinical • P3 data • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Migraine • Nephrology • Pain

Real wold experience of atogepant in 72 patients with chronic migraine and daily headache (AtoOnly Consortium) (EHF-EHC 2025) - "According to the local guidelines, Atogepant is approved in patients with prior failure to three or more migraine preventive drugs, including onabotulinumtoxinA. Atogepant discontinuation concerning tolerability was no different among groups. Patients with Chronic Migraine and Daily Headache has a poorer response to Atogepant, athough more than one third achieved a good response at three months."

Clinical • CNS Disorders • Migraine • Mood Disorders • Pain

Rapid delta-band functional connectivity changes in HD-EEG after one month of atogepant in migraine patients (EHF-EHC 2025) - "12 patients with high-frequency episodic migraine (HFEM;n=7) or chronic migraine (CM;n=5) underwent HD-EEG recordings at two time points:before starting Atogepant (T0) and after one month of therapy(T1).15 healthy controls(HC) were also enrolled.Clinical evaluations included: monthly migraine days, monthly symptomatic drugs intake, modified Migraine Disability Assessment, the headache impact test(HIT-6), the Migraine-Specific Quality of Life Questionnaire, the 12-item Allodynia Symptom Checklist, and the Migraine Interictal Burden Scale.EG-based FC was analyzed in source space using the weighted Phase Lag Index (wPLI) across δ,θ,α,β,low-γ, and high-γ bands. Compared to HCs, HFEM+CM patients exhibited increased δ band FC in temporo-parietal,orbitofrontal,insular,and limbic regions.At T1 a significant reduction in this aberrant FC was observed,particularly in bilateral temporo-parietal,cingulate,insular, and prefrontal cortices.Baseline δ-band FC correlated with greater..."

Clinical • CNS Disorders • Migraine • Pain