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

AbbVie Beats on Q2 Earnings & Sales, Stock Up on Raised '25 EPS View (Yahoo Finance) - "Sales from the neuroscience portfolio increased 24% to $2.68 billion, driven by higher sales of Botox Therapeutic, depression drug Vraylar and migraine drugs Ubrelvy and Qulipta. Neuroscience sales beat the Zacks Consensus Estimate and our model estimate of $2.47 billion and $2.48 billion, respectively. While Botox Therapeutic sales rose 14.2% to $928 million, sales of Vraylar increased 16.3% to $900 million. Sales of Ubrelvy totaled $338 million, up 47.2%. Qulipta sales increased 76.9% to $267 million. Sales of Vyalev, the recently approved transformative therapy for advanced Parkinson’s disease, totaled $98 million, compared with $63 million in the first quarter."

Sales • Depression • Migraine • Pain • Parkinson's Disease

One-month atogepant treatment induces rapid changes in delta-band functional connectivity in migraine: an HD-EEG study. (PubMed, J Headache Pain) - "This pilot study provides preliminary evidence that atogepant modulates δ band functional brain connectivity after one month of treatment in patients with episodic and chronic migraine. These changes in central brain networks are associated with clinical improvement and may serve as a neurophysiological marker of CGRP receptor antagonist efficacy. Larger-scale studies are needed to confirm and extend these findings."

Journal • Review • CNS Disorders • Migraine • Pain

One-month atogepant treatment induces rapid changes in delta-band functional connectivity in migraine: an HD-EEG study (J Headache Pain) - P=NA | N=37 | "Twelve 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 administration (T0) and after one month of treatment (T1). Fifteen healthy controls (HC) were also enrolled....Compared to HCs, HFEM + CM patients exhibited increased δ band functional connectivity (FC) in temporo-parietal, orbitofrontal, insular, and limbic regions. After one month of atogepant treatment, 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 disability (mMIDAS, MSQ), while treatment-induced FC changes (ΔmNC) were associated with improvements in mMIDAS, HIT-6, and ASC-12 scores, highlighting the clinical relevance of δ band network modulation."

Clinical data • Migraine

The state of insurance coverage of calcitonin gene-related peptide-targeted medications and its impact on the implementation of the American Headache Society's 2024 consensus statement: An interrupted time-series analysis. (PubMed, Headache) - "Ten months after the American Headache Society's March 2024 consensus statement made the CGRP-targeted medications first-line for the prevention of migraine, insurance companies have had incomplete compliance with the recommendations, potentially limiting the full impact of the AHS' consensus statement on the utilization of the CGRP-targeted therapies."

Journal • Reimbursement • US reimbursement • CNS Disorders • Migraine • Pain

Comparative Effectiveness of Migraine Preventive Medications: The APT Comparison Study (clinicaltrials.gov) - P4 | N=1335 | Recruiting | Sponsor: Mayo Clinic | Not yet recruiting ➔ Recruiting

Enrollment open • HEOR • CNS Disorders • Migraine • Pain

Early Experience Treating Vestibular Migraine with Small Molecule CGRP Antagonists (AAO-HNSF 2025) - "The gepants used included ubrogepant, rimegepant, atogepant, and zavegepant. Gepants can be effective medications for the treatment of vestibular migraine."

CNS Disorders • Migraine • Otorhinolaryngology • Pain • Vertigo

Dual calcitonin gene-related peptide antagonists for chronic migraine prevention (AHS 2025) - "These medications are divided into monoclonal antibodies, "-mAbs" (erenumab, fremanezumab, galcanezumab, and eptinezumab) and small molecule "-gepants" (rimegepant and atogepant)...Common prior or concurrent non-CGRP antagonist migraine preventive medications included topiramate (84%), tricyclic antidepressants (76%), and onabotulinumtoxinA (73%)... In our small sample, dual preventive CGRP antagonist use was well-tolerated and may be considered for patients with chronic migraine who are resistant to usual treatment. However, larger studies are needed to confirm the safety and efficacy of this approach."

CNS Disorders • Depression • Migraine • Mood Disorders • Pain • Psychiatry

Longitudinal effects of CGRP pathway-targeting migraine therapies on blood pressure and body mass index: A 12-month retrospective analysis (AHS 2025) - " Using data from electronic health records at Jefferson Headache Center, we conducted a retrospective study of adult patients with naïve use of either gepants (atogepant, rimegepant) or CGRP mAbs (erenumab, fremanezumab, galcanezumab) for migraine prevention. These findings suggest that most CGRP pathway-targeting migraine medications have negligible effects on monthly changes in BP over one year. These BP differences were small in magnitude and of unclear clinical significance. Study limitations include the unbalanced distribution of medications and potential changes in antihypertensive medication regimens during the one-year study period that could not be fully captured in our model."

Retrospective data • CNS Disorders • Migraine • Pain

Real-world switch rates of injectable migraine preventive therapies in patients with chronic migraine (AHS 2025) - "The primary endpoint was treatment switching, defined by the occurrence of ≥1 claim for a different branded migraine preventive treatment (onabotA, CGRP mAb, or atogepant) in the 12 months following the index date... A total of 1869 patients met the study inclusion criteria, of which 723 initiated onabotA and 1146 initiated a CGRP mAb (303 erenumab, 308 fremanezumab, 517 galcanezumab, 18 eptinezumab) as their index therapy... Chronic migraine patients on a CGRP mAb were significantly more likely to switch to a different branded migraine preventive treatment within 12 months of treatment initiation compared to those on onabotA."

Clinical • Real-world • Real-world evidence • CNS Disorders • Migraine • Pain

An interdisciplinary approach to medication overuse headache: A case study (AHS 2025) - "She had tried and failed Botulinum toxin injections, occipital nerve blocks and trigger point injections, sphenopalatine ganglion blocks, Amitriptyline, Propranolol, Venlafaxine, Emgality, Aimovig, Vyepti, Qulipta, and Cefaly. The interdisciplinary model with headache neurology, occupational therapy, pain psychology, and physical therapy allowed for continued reinforcement and collaborative integration to allow for a more in-depth assessment of the barriers contributing to medication overuse headache and the implementation of a successful, sustainable plan. The patient was successfully able to stop Excedrin and reduce Sumatriptan use significantly, implement self-regulation and cognitive strategies for pain and anxiety management, and reduce her monthly headache and migraine days by more than 75%. Emotion wheel"

Case study • Clinical • CNS Disorders • Cognitive Disorders • Depression • Migraine • Mood Disorders • Musculoskeletal Pain • Neuralgia • Pain • Psychiatry

Characteristics and eptinezumab infusion experience in participants in whom ≥1 prior preventive anti-CGRP treatment had failed: Interim results of an ongoing real-world study (AHS 2025) - "INFUSE includes adults ≥18 years of age with a diagnosis of migraine in whom ≥1 preventive a-CGRP treatment had failed (erenumab, fremanezumab, galcanezumab, atogepant, or rimegepant [prescribed every other day]). Results of this interim analysis of the INFUSE study indicate that individuals with migraine initiating eptinezumab treatment after ≥1 prior a-CGRP preventive treatment had failed typically have a long history of disease, severe migraine, and have cycled through three or more a-CGRP preventive treatments. The level of concern about initiating an IV treatment was low, and participants generally had a positive infusion experience."

Clinical • Real-world • Real-world evidence • CNS Disorders • Migraine • Pain • Psychiatry

Patient preferences for the preventive treatment of episodic migraine in the United States: A discrete-choice experiment. (PubMed, Headache) - "Relative importance estimates suggest that, on average, respondents with episodic migraine preferred an oral pill over monthly or quarterly injections and infusions. Respondents also preferred to avoid treatment-related nausea and constipation. The predicted choice probability results further suggest a preference for a daily oral pill, given that seven of 10 respondents, on average, would prefer a profile similar to atogepant over profiles similar to monoclonal antibodies administered intravenously or by self-injection."

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

Adverse events associated with gepants: a pharmacovigilance analysis based on the FDA adverse event reporting system. (PubMed, J Headache Pain) - "The present pharmacovigilance study systematically revealed the significant risk signals of gepants. The common AEs and unique AEs of the four gepants were also identified and explored. Our results would provide valuable reference for the safe use of gepants, guiding personalized drug selection in clinical practice."

Adverse events • Journal • CNS Disorders • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Migraine • Pain

Evaluation of unmet needs and quality-of-care indicators among patients with migraine in the United States: 2021–2022 (AHS 2025) - "Following migraine QOC indicators selected based on current literature were assessed among diagnosed migraine patients: (1) migraine-related healthcare visits: emergency department (ED), urgent care, neurology, primary care, outpatient, inpatient hospitalizations in each full calendar year, and 30-day hospital readmission following the first hospitalization; (2) medication use: acute (generic [triptans, opioids, NSAIDs, ergotamines, barbiturates, and acetaminophen] and branded [Ubrogepant, Zavegepant, Lasmiditan, Rimegepant (when the first prescription is for less or equal to 8 pills)]) and preventive (oral migraine preventive medications[OMPM; anticonvulsants, antidepressants, antihypertensives, and other oral combination medications] and branded [CGRP mAbs, Botox, Atogepant, Rimegepant (when the first prescription is for >8 pills)]) migraine treatments; (3) other migraine-related diagnoses: acute medication overuse (AMO) based on medication utilization algorithm and..."

Clinical • CNS Disorders • Migraine • Pain

Network meta-analysis comparing efficacy and safety outcomes of atogepant, rimegepant, and galcanezumab in patients with episodic migraine after including CHALLENGE-MIG trial (AHS 2025) - " The NMA included 5 randomized, controlled trials for the preventive treatment of EM (ADVANCE [atogepant 60 mg], BHV3000-305 [rimegepant 75 mg], EVOLVE-1, EVOLVE-2 [galcanezumab 120 mg], and CHALLENGE-MIG [rimegepant 75 mg, galcanezumab 120 mg]). Atogepant 60 mg demonstrated significant improvements in 3 of the 4 efficacy outcomes compared to rimegepant 75 mg and significantly increased odds of achieving ≥50% RR in MMD relative to galcanezumab 120 mg. Other efficacy outcomes were not significantly different. Atogepant 60 mg demonstrated comparable all-cause d/c and TEAEs relative to rimegepant and galcanezumab."

Retrospective data • CNS Disorders • Migraine • Pain

Number needed to treat analysis of atogepant compared to rimegepant for the preventive treatment of episodic migraine in Japanese and global participants (AHS 2025) - P2/3, P3 | "One analysis evaluated this outcome using data from the Japanese only trials for atogepant [RELEASE (NCT05861427), placebo, N = 134; atogepant 60 mg, N = 132] and rimegepant [BHV3000-309 (NCT05399485), placebo, N = 244, rimegepant 75 mg, N = 240], and a second analysis evaluated this outcome using data from global (Japan and US) trials for atogepant [ADVANCE (NCT03777059), placebo, N = 222; atogepant 60 mg, N = 231, and RELEASE] and rimegepant [BHV3000-305 (NCT03732638), placebo, N = 371; rimegepant 75 mg, N = 370, and BHV3000-309]. Atogepant had substantially lower NNTs versus placebo than rimegepant for the preventive treatment of EM across the Japanese only trials and global trials. An additional 7–14 individuals would need to be treated with rimegepant 75 mg to result in a comparable response with atogepant 60 mg. These results suggest that atogepant may be more efficacious than rimegepant for the preventive treatment of EM."

Clinical • CNS Disorders • Migraine • Pain

Milk and plasma pharmacokinetics of single-dose atogepant in healthy lactating women (AHS 2025) - "Atogepant average milk:plasma concentration ratio was 0.076 following a 60mg dose in lactating women. Based on lack of atogepant accumulation upon daily dosing, the low cumulative amount of atogepant excreted in breast milk and the low RID of 0.189%, atogepant may be considered, for the preventive treatment of migraine in lactating women. TABLE 1."

Clinical • PK/PD data • CNS Disorders • Migraine • Pain

Economic impact of early versus late initiation of atogepant for the preventive treatment of migraine (AHS 2025) - "Reducing 2-step edits/1-step edit to 0-step edits for atogepant demonstrated annual cost savings of more than $1000 per patient for US payors. These model-based estimates should be assessed in randomized trials of benefit designs."

HEOR • CNS Disorders • Migraine • Pain

Atogepant demonstrates greater improvement in function using the Activity Impairment in Migraine-Diary (AIM-D) during interictal days: Post-hoc analysis from the PROGRESS chronic migraine trial (AHS 2025) - "Participants with CM and at least a little baseline impairment demonstrated significant improvement in both AIM-D domains (PDA and PI) on interictal days, compared to placebo. On interictal days, participants taking placebo sometimes demonstrated a worsening of AIM-D domain scores (e.g., PDA score in month 1, and PI score in all three months). Our findings suggest that treatment with atogepant 60 mg once daily effectively reduces interictal burden and minimizes the disruptive effects of migraine between attacks."

Retrospective data • CNS Disorders • Migraine • Pain

Real-world effectiveness, treatment optimization, and satisfaction of ubrogepant for the acute treatment of migraine in individuals taking atogepant for the preventive treatment of migraine: Results from the COURAGE II study (AHS 2025) - "Real-world use of ubrogepant for acute treatment was effective when used in combination with atogepant for preventive treatment as indicated by high rates of meaningful pain relief and restoration of function within 4h, significant association with experiencing acute treatment optimization, and high rates of treatment satisfaction. No new safety signals were identified. Percentage of ubrogepant-treated migraine attacks for which meaningful pain relief (MPR) and return to normal function (RNF) within 2 and 4 h was reported in respondents who used atogepant concomitantly for the preventive treatment of migraine."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • CNS Disorders • Migraine • Pain

Impact of atogepant on activity limitations stratified by patient global impression of change responders and non-responders: Post hoc analyses of three pivotal trials (AHS 2025) - "PGIC responders with EM (ADVANCE), EM with prior inadequate responses to treatment (ELEVATE), and CM (PROGRESS) were significantly more likely to achieve no/little limitations in activity across weeks 1–12 when taking atogepant 60 mg once daily, relative to placebo. Our findings suggest that atogepant 60 mg once daily users who were PGIC responders demonstrated significantly greater reduction (i.e., improvement) in limitations in activity, relative to placebo in these post-hoc analyses. These results indicate that PGIC responders show substantial improvements in functional status as validated with daily diary measures."

Clinical • Retrospective data • CNS Disorders • Migraine • Pain

Impact of atogepant on migraine headache severity for the preventive treatment of episodic migraine: A post-hoc analysis of the 12-week ADVANCE and 52-week open-label trials (AHS 2025) - "Atogepant reduced the number of monthly moderate/severe migraine headache days and mean pain severity of migraine headache days compared with placebo in ADVANCE, and reductions were consistent across 52 weeks in the open-label trial."

Clinical • Retrospective data • CNS Disorders • Migraine • Pain

Oral atogepant mitigates spreading depolarization–induced pain and anxiety behavior in mice (AHS 2025) - "These data suggest SD provokes a reproducible and robust pain phenotype in mice that is alleviated by pre-administration with atogepant. There was also improvement in SD-induced anxiety-like behavior following atogepant."

Preclinical • CNS Disorders • Migraine • Mood Disorders • Pain • Psychiatry • THY1

Small-molecule CGRP antagonist atogepant does not alter cortical spreading depression susceptibility in rats (AHS 2025) - "These data suggest that Atogepant efficacy in preventing migraines is unrelated to CSD suppression. While CSD is known to disrupt the BBB, we have not measured brain atogepant levels. Therefore, it is possible that the lack of an effect on CSD susceptibility may be because of insufficient brain levels reached despite the BBB disruption."

Preclinical • CNS Disorders • Depression • Migraine • Mood Disorders • Pain • Psychiatry

AbbVie Announces New Data Demonstrating Atogepant (QULIPTA / AQUIPTA) Achieves Superiority Across All Endpoints in Phase 3 Head-to-Head Study Compared to Topiramate for Migraine Prevention (PRNewswire) - P3 | N=545 | TEMPLE (NCT05748483) | Sponsor: AbbVie | "The study met the primary endpoint of treatment discontinuation due to adverse events (AEs), demonstrating that atogepant, a calcitonin gene-related peptide (CGRP) receptor antagonist, had fewer discontinuations due to AEs than topiramate, an anticonvulsant medication also approved for migraine prevention. Over the 24-week double-blind treatment period, discontinuation due to AEs was significantly lower with atogepant (12.1%) compared to topiramate (29.6%), representing a relative risk of 0.41 (95% CI: 0.28, 0.59; p<0.0001)....The study also met all six secondary endpoints, including a key measure of clinical efficacy: 64.1% of patients on atogepant achieved a ≥50% reduction in mean monthly migraine days (MMD) during months 4 to 6 of the double-blind treatment period compared to 39.3% of patients on topiramate (p<0.0001)....Full results from the TEMPLE study will be presented at an upcoming medical meeting."

P3 data: top line • Migraine