Ajovy (fremanezumab-vfrm) / Otsuka, Teva - LARVOL DELTA

Key Innovative brands continued to drive growth and provide value for patients, with 2025 revenues surpassing $3 billion, +35% YoY in LC (Teva Press Release) - "AUSTEDO global revenues of $2.26 billion, growing 34% YoY in LC. AJOVY global revenues of $673 million, up 30% YoY in LC. UZEDY revenues of $191 million, up 63% YoY in LC; underscoring Teva's commitment to drive new advances in neuroscience."

Sales • Huntington's Disease • Migraine • Pain • Schizophrenia

Botulinum Toxin Type A for the Prevention of Migraines: An Umbrella Review of Systematic Reviews. (PubMed, Toxins (Basel)) - "Overall, quantitative evidence indicated favorable effects of BoNT-A compared with placebo for chronic migraines, across headache frequency, headache severity, and acute medication use, but less efficacy than topiramate and the CGRP monoclonal antibodies (CGRPmAbs) galcanezumab and fremanezumab. Although botulinum toxin type A is widely used as a preventive treatment for chronic migraines, the available evidence supports its efficacy at a moderate level. Further head-to-head and long-term analyses are needed to clarify its comparative role alongside newer biologic treatments."

Journal • Review • CNS Disorders • Migraine • Pain

Reduced Frequency of Prolonged Sporadic Hemiplegic Migraine Attacks Following Fremanezumab Treatment-A Case Report. (PubMed, Eur J Neurol) - "This case illustrates the diagnostic complexity of SHM and adds to the growing body of anecdotal observations suggesting that CGRP monoclonal antibodies may be a promising preventive treatment for patients with HM. Further studies are needed to evaluate their efficacy in this rare migraine subtype."

Journal • Cardiovascular • CNS Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Migraine • Non-Hodgkin’s Lymphoma • Oncology • Pain • Transplantation

Fremanezumab, Migraine and Sleep (clinicaltrials.gov) - P4 | N=22 | Terminated | Sponsor: Beth Israel Deaconess Medical Center | N=100 ➔ 22 | Recruiting ➔ Terminated; We could not recruit enough patients who fulfilled inclusion criteria and eventually gave up and terminated the study. The reason for not closing it is that we did have

Enrollment change • Trial termination • CNS Disorders • Migraine • Pain • Sleep Disorder

Drugs for Migraine Prophylaxis. (PubMed, Dtsch Arztebl Int) - "The new prophylactic drugs against migraine are effective, well-tolerated, and especially useful for patients for whom traditional oral migraine prophylactic drugs and onabotulinum toxin A are ineffective, not tolerated, or contraindicated."

Journal • CNS Disorders • Migraine • Pain

Efficacy and safety of CGRP monoclonal antibodies for migraine prevention in episodic migraine; a network Meta-analysis. (PubMed, Eur J Clin Pharmacol) - "fremanezumab offers the best balance of efficacy and safety. Further long-term studies are needed."

Clinical • Journal • Retrospective data • Review • CNS Disorders • Migraine • Pain

A 12-month observational study on the safety, efficacy on migraine-associated symptoms and satisfaction of CGRP monoclonal antibodies in Japanese patients with migraine. (PubMed, J Neurol Sci) - "This study highlighted the role of early response in predicting the long-term response to CGRP mAbs. We also emphasized the importance of documenting satisfaction, migraine aura frequency, in addition to migraine frequency, for deeper insights into migraine pathophysiology."

Journal • Observational data • CNS Disorders • Migraine • Pain

Fremanezumab in Children and Adolescents with Episodic Migraine. (PubMed, N Engl J Med) - P3 | "Among children and adolescents with episodic migraine, fremanezumab resulted in greater reductions in the number of migraine days and headache days than placebo. Injection-site erythema was the most common adverse event with fremanezumab. Longer follow-up is required to further understand the efficacy and safety of the drug in this population. (Funded by Teva Pharmaceuticals; ClinicalTrials.gov number, NCT04458857.)."

Clinical • Journal • CNS Disorders • Dermatology • Migraine • Pain

AJOVY (fremanezumab-vfrm) Significantly Reduced Monthly Migraine and Headache Days in Children and Adolescents with Episodic Migraine Compared to Placebo in the SPACE Trial; Results Published in New England Journal of Medicine (GlobeNewswire) - "In the SPACE trial, AJOVY reduced monthly migraine days (MMD) by 2.5 days compared to 1.4 days with placebo (difference: 1.1 days; P = 0.02) and reduced monthly headache days (MHD) of at least moderate severity by 2.6 days versus 1.5 days (difference: 1.1 days; P = 0.02). A significantly higher proportion of participants achieved a ≥ 50% reduction in MMD (47.2%) with AJOVY compared to placebo (27.0%) (P = 0.002)."

P3 data • Migraine • Pain

A Study to Test if Fremanezumab is Effective in Preventing Migraine in Children and Adolescents (clinicaltrials.gov) - P3 | N=506 | Completed | Sponsor: Teva Branded Pharmaceutical Products R&D LLC | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Migraine • Pain • Pediatrics

Comparative effects of anti-CGRP monoclonal antibodies and atogepant on migraine disability, sleep quality, and attack frequency: A 12-month observational study (EHF-EHC 2025) - " This retrospective observational study included patients with chronic migraine refractory to first-line preventives, treated with erenumab, galcanezumab, fremanezumab, or atogepant. Anti-CGRP therapies reduced migraine burden in patients with refractory chronic migraine. Notably, erenumab was associated with a strong correlation between disability and sleep quality. Atogepant showed promising early improvements in sleep in selected patients."

Clinical • Observational data • CNS Disorders • Migraine • Pain • Sleep Disorder

Combining anti-CGRP antibodies with atogepant: Safety and efficacy in a patient cohort (EHF-EHC 2025) - "Treatments included erenumab (n=1), fremanezumab (n=11), galcanezumab (n=6), and eptinezumab (n=9). In this real-world cohort, combining antiCGRP mAbs with atogepant appears to be safe and may offer additional benefit."

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

Real-world evaluation of rimegepant usage and switch patterns in a single tertiary headache center (EHF-EHC 2025) - "Figure 1 illustrates the monthly utilization of rimegepant with/without onabotulinumtoxinA or other CGRP mAbs...Among those switches, galcanezumab (93) and fremanezumab (60) were the most common immediate prior CGRP preventives...Among those, there were 80 switches to atogepant and 59 to fremanezumab... Real-world data demonstrate rimegepant's versatility as both acute and preventive therapy. Its dual indication enables flexible dosing strategies, serving as a preventive for CGRP-naïve patients and as an effective CGRP preventive option within treatment algorithms. Fig."

Clinical • HEOR • Real-world • Real-world evidence • CNS Disorders • 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). Real-world efficacy broadly aligns with clinical trial data, though our galcanezumab findings are limited by small sample size. While direct comparisons outside of randomised trials are limited, agents differed in both effectiveness and tolerability. Rimegepant was well tolerated but was associated with the lowest effectiveness at 12 weeks."

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. More than half of our patients reported significant improvement with antiCGRP therapy. Selfreported adverse events were more frequent (56%) than previously reported. Most frequent, were gastrointestinal symptoms and local skin reactions."

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

Middle meningeal artery lidocaine infusion for refractory migraine: First case report in Portugal (EHF-EHC 2025) - "Various pharmacologic classes were tried without benefit: antihypertensives and calcium channel blockers (propranolol, candesartan, flunarizine), antiepileptics (valproic acid, topiramate, oxcarbazepine), antidepressants (amitriptyline, nortriptyline, venlafaxine, fluvoxamine, sertraline, clomipramine), other preventives (prednisolone, oxitriptan, melatonin), cycles of botulinum toxin (PREEMPT protocol), monoclonal antibodies (galcanezumab, fremanezumab, erenumab), and atogepant. At the time of the procedure, the patient was on eptinezumab 100 mg and botulinum toxin every three months but continued to have daily headaches, with severe intensity and reliance on eletriptan for acute relief... MMA lidocaine infusion has been described in few cases, and this is, to our knowledge, the first reported in Portugal. It constitutes an invasive therapeutic approach that should be considered only as a rescue option for carefully selected patients with severely refractory migraine...."

Case report • Clinical • Anorexia • CNS Disorders • Migraine • Pain

Local cutaneous complications of CGRP monoclonal antibodies: A case series (EHF-EHC 2025) - " Nine women treated with subcutaneous antiCGRP 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... Local cutaneous reactions to subcutaneous anti-CGRP monoclonal antibodies occurred in nearly 5% of patients and were generally mild. 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..."

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

Hanmi Pharmaceutical announced Tuesday that it has signed a business agreement with Teva Handok for the domestic distribution and sales of Ajovy, and will commence distribution and promotional activities starting this month. (Korea Biomedical Review) - "Hanmi Pharmaceutical and Teva Handok aim to strengthen their partnership to deliver innovative neurological therapies to Korean patients more efficiently."

Licensing / partnership • Migraine

Decoding the long-term safety of anti-CGRP (receptor) mAbs: a meta-analysis and systematic review. (PubMed, J Headache Pain) - No abstract available

Journal • Retrospective data • Review • CNS Disorders • Migraine • Pain

COACT study: CGRPmAbs + OnabotulinumtoxinA assessment of chronic migraine treatments study (EHF-EHC 2025) - "The addition of fremanezumab to onabotulinumtoxinA resulted in significant reductions in monthly migraine days at 12 weeks and 24 weeks (p <0.001). Significant reductions in HIT-6 scores at 12 weeks and 24 weeks were also seen. These findings support the use of CGRP mAbs and onabotulinumtoxinA for the preventive treatment of chronic migraine."

CNS Disorders • Migraine • Pain

Short-term longitudinal white matter structural changes in patients with migraine with 12-week positive response to fremanezumab (EHF-EHC 2025) - "Fremanezumab causes short-term localized white matter longitudinal changes in patients with migraine with positive response. Fig. 1 Fig."

Clinical • CNS Disorders • Migraine • Pain

CGRP, VIP and PACAP plasmatic levels in migraine patients before and after anti-CGRP(R) monoclonal antibodies prophylaxis (EHF-EHC 2025) - " From Feb 2022 to Feb 2023, we enrolled 56 migraineurs who began prophylaxis with erenumab (n=26), galcanezumab (n=16), or fremanezumab (n=14). Anti-CGRP(R) mAbs are very effective migraine prophylactic agents. Galcanezumab significantly reduced plasma CGRP by 3 months, with near-undetectable levels at 6 months, consistent with its CGRP-binding mechanism and prior studies. In contrast, erenumab did not affect significantly CGRP plasmatic levels, potentially due to its different binding site on the CGRP receptor."

Clinical • CNS Disorders • Migraine • Pain • ADCYAP1

Migraine prevention with Fremanezumab: Efficacy assessment (EHF-EHC 2025) - "FRM demonstrares sustained long-term efficacy and significant clinical benefits, including in patients with comorbidities like depression and medication overuse. Its innovative mechanisms and favorable pharmacokinetics make it a promising option for migraine prevention."

Clinical • CNS Disorders • Depression • Liver Failure • Migraine • Nephrology • Pain • Renal Disease

Discontinuation of anti-calcitonin Gene-Related Peptide (CGRP) monoclonal Antibodies (mAbs) in migraine patients after 12 months of good response: Are there any predictors of restarting mAbs need? Real-world cohort of 103 patients (EHF-EHC 2025) - "They received fremanezumab (n=77) or galcanezumab (n=26) for a median of 25.9 months (IQR 15.6–39.7). In this real-world cohort, nearly half of the patients who discontinued anti-CGRP monoclonal antibodies after a sustained good response eventually required resuming treatment. No clinical or demographic predictors were identified, supporting individualized decisions and close follow-up."

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

Reporting of lack of efficacy of anti-CGRP monoclonal antibodies in migraine patients treated with other concomitant monoclonal antibodies: A VigiBase disproportionality analysis (EHF-EHC 2025) - " Reports listing erenumab, galcanezumab, fremanezumab, or eptinezumab as suspected or interacting drugs and collected in VigiBase up to March 9th, 2025 were included and classified as cases (reporting lack of efficacy) or non-cases (reporting other adverse drug reactions). The concomitant use of other mAbs in patients receiving anti-CGRP mAbs for migraine is not associated with increased reporting of lack of efficacy in VigiBase. These findings offer preliminary reassurance regarding the real-world effectiveness of anti-CGRP mAbs when administered in combinations with mAbs for other indications."

Clinical • CNS Disorders • Migraine • Pain