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

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 date: Dec 2025 ➔ Sep 2025

Trial completion • Trial completion date • CNS Disorders • Migraine • Pain • Pediatrics

Safety outcomes from a Phase 3, randomized, double-blind, placebo controlled study of fremanezumab for the preventive treatment of migraine in Chinese adults (IHC 2025) - "AE, adverse event; DBP, double-blind period; QM, monthly; Q3M, quarterly; SAE, serious adverse event; TRAE, treatment‑related adverse event. Conclusion This study showed that fremanezumab could be an effective and well-tolerated preventive migraine treatment option for this population."

Clinical • P3 data • CNS Disorders • Migraine

Retreatment After Discontinuation of Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies in Migraine: Are There Any Predictors? Insights from a Real-World Cohort (IHC 2025) - "They received fremanezumab (n=77) or galcanezumab (n=26) for a median of 25.9 months (IQR 15.6–39.7). Conclusion In this real-world cohort, nearly half of the patients who discontinued anti-CGRP monoclonal antibodies after a sustained good response eventually required retreatment. No clinical or demographic predictors were identified, supporting individualized decisions and close follow-up."

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

Fremanezumab in migrane patients: promising results, but still without clinical significance (IHC 2025) - "t = -0.60, df = 10, p-value = 0.5640). Eleven randomized clinical trials involving 5,961 patients were included: three RCTs evaluating episodic migraine exclusively, four evaluating chronic migraine and five evaluating both. In studies evaluating patients with episodic migraine, the reduction in monthly headache days of at least moderate severity subtracted from placebo (mean difference) was -0.26 (95% CI - 0.60 to 0.09; fremanezumab n = 532 vs."

Clinical • CNS Disorders • Migraine

Long term persistence of onabotulinumtoxinA versus calcitonin gene-related peptide monoclonal antibodies in new initiators with chronic migraine (IHC 2025) - "Methods This retrospective observational study of adult patients with CM using Merative Marketscan Commercial and Medicare database included new initiators of onabotA or a CGRP mAb (erenumab, fremanezumab, galacanezumab, eptinezumab) who stayed on index treatment from 12 to 24 months. A significantly higher persistence with onabotA continued through 18 months (38.1% vs 29.8%; OR: 0.69 [95% CI: 0.61-0.78]; P<0.001), and 24 months (32.1% vs 23.0%; OR: 0.63 [95% CI: 0.54-0.74]; P<0.001). Conclusion This retrospective claims analysis demonstrated that patients with CM who initiate onabotA are more likely to remain persistent on therapy at all long-term time points for up to 24 months compared with patients with CM who initiate a CGRP mAb."

CNS Disorders • Migraine

Unmasking Hypnic Headache After Withdrawal from Medication Overuse: Two Case Reports (IHC 2025) - "Methods Case 1: A 68-year-old male developed daily headaches around age 50 and used diclofenac and ergotamine/caffeine three to four times daily for 15 years...He failed flunarizine (1 month), topiramate (2 months), and a single dose of fremanezumab...Previous preventive treatments (propranolol and imipramine) were ineffective...Preventive therapy plays a key role. Without it, reliance on acute medications may lead to recurrent medication overuse headache."

Case report • Clinical • CNS Disorders • Migraine

Super-responders (>75% response rate) to anti-CGRP monoclonal antibodies after one year of treatment: a multicenter, prospective, observational study (IHC 2025) - "Methods This multicenter (n=16), prospective real-life study included all consecutive adults with high-frequency episodic (HFEM: 8-14 days/month) or chronic migraine (CM) who had failed >3 prior preventives and were treated with erenumab, fremanezumab, or galcanezumab for >12 months. While 29.4% were early super-responder, 40.6% became super-responders between months 4 and 12. Ultra-late super-responders exhibit fewer symptoms of peripheral ((pain intensity, pain site, unilateral cranial symptoms) and central (ictal allodynia) sensitization compared to early and late super-responders."

Clinical • Observational data • CNS Disorders • Migraine

Use of Fremanezumab in Children with Refractory Chronic Migraine: A Case Series (IHC 2025) - "All patients had a body weight above 45 kg and had previously undergone multiple oral preventive treatments, including amitriptyline, topiramate, divalproex sodium, gabapentin and flunarizine, without satisfactory response. Conclusion Fremanezumab was shown to be safe and effective in pediatric patients with chronic migraine refractory to oral preventive therapies and presenting with medication overuse. Although few studies have focused on this age group, this case series suggests that fremanezumab may be a promising therapeutic alternative in specific and supervised clinical contexts."

Clinical • CNS Disorders • Migraine

Erenumab in treatment of migraine patients with psoriasis – two case reports (IHC 2025) - "Given the suspected association with erenumab, therapy was discontinued and later switched to fremanezumab, a monoclonal antibody targeting CGRP itself rather than its receptor. Although erenumab is generally well tolerated, its receptor-specific mechanism may, in certain individuals, modulate immune pathways in a manner that aggravates pre-existing inflammatory conditions. Further prospective studies are needed to better define the safety profile of CGRP inhibitors, particularly in patients with comorbid immune-mediated diseases."

Case report • Clinical • CNS Disorders • Migraine

Two-year adherence and efficacy of 675-mg Fremanezumab on Chronic, Episodic, and Medication-Overuse Headaches (IHC 2025) - "The average reductions in monthly acute medication days after two years for CM, EM, and MOH groups were -6.0,-13.2, -3.1, and -9.8 at 24 months. Conclusion Our study reveals that fremanezumab (675-mg every three months) effectively reduces headache severity and acute medication use across all migraine types."

Adherence • Clinical • CNS Disorders • Migraine

MONOCLONAL ANTIBODIES TARGETING THE CALCITONIN GENE-RELATED PEPTIDE FOR THE TREATMENT OF PERSISTENT POST-TRAUMATIC HEADACHE: A LITERATURE REVIEW (IHC 2025) - "Phase III clinical trials with fremanezumab — a fully humanized mAb that inhibits CGRP — showed significant efficacy in reducing monthly migraine days with both monthly and quarterly dosing regimens...Conclusion Monoclonal antibodies targeting CGRP represent a promising therapeutic approach for persistent post-traumatic headache, offering substantial clinical benefits and a favorable safety profile. Given the strong involvement of CGRP in migraine pathophysiology, further studies are warranted to better define the role of this treatment, especially in complex populations such as adolescents and patients with comorbid conditions."

Review • CNS Disorders • Migraine

Prescription of monoclonal antibodies against calcitonin gene-related peptide for the prophylaxis of migraine in Austria: a retrospective, longitudinal analysis of nationwide insurance data (IHC 2025) - "Methods Based on the nation-wide database of the Austrian Social Insurances, we included all persons with a dispensation of erenumab, galcanezumab, or fremanezumab from 1 September 2018 to 30 September 2022 and investigated: therapy breaks, switches, the dispensation of triptans, other acute prescription medications, and of other migraine preventatives before, during and after the dispensation of CGRP-Ab, the proportion of days covered. The proportion of days covered was 96 %. Conclusion This first nation-wide pharmacoepidemiologic study showed that within 49 months persistence to CGRP-Ab was excellent, the majority resumed CGRP-Ab soon after a therapy break, and the dispensation of triptans and other preventatives decreased during treatment with CGRP-Ab."

Reimbursement • Retrospective data • US reimbursement • CNS Disorders • Migraine

Long term persistence of patients with chronic migraine switching to onabotulinumtoxinA or a different calcitonin gene-related peptide monoclonal antibody (CGRP mAb) after initial CGRP mAb treatment (IHC 2025) - "Methods This retrospective observational study of adults with CM using Merative Marketscan Commercial and Medicare database included patients who had ≥1 claims of a CGRP mAb, then initiated another CGRP mAb (erenumab, fremanezumab, galacanezumab, eptinezumab) or onabotA for 12-24 months post-index. A significantly higher persistence with onabotA continued through 18 months (46.2% vs 25.9%; OR: 0.41 [95% CI: 0.33, 0.51]; P < 0.001), and 24 months (35.1% vs 17.8%; OR: 0.40 [95% CI: 0.30, 0.54]; P < 0.001). Conclusion This retrospective, real-world study demonstrated that patients with CM who switched to onabotA treatment after an initial CGRP mAb were more likely to remain persistent on therapy for 12-24 months compared to patients with CM who switched to another CGRP mAb."

Clinical • CNS Disorders • Migraine

SYSTEMATIC REVIEW OF THE SAFETY OF ANTI-CGRP MONOCLONAL ANTIBODIES (ERENUMAB, EPTINEZUMAB, FREMANEZUMAB, GALCANEZUMAB) IN PRIMARY AND SECONDARY HEADACHES (IHC 2025) - "Conclusion Anti-CGRP monoclonal antibodies show a favorable safety profile, with predominantly mild to moderate adverse events consistent with their drug class and administration route. The low discontinuation rate and non-serious nature of most effects support their tolerability and safe clinical use in headache patients."

Clinical • Review • CNS Disorders • Migraine

Is fremanezumab effective in improving quality of life in people with headache? (IHC 2025) - "t = -0.48, df = 2, p-value = 0.6785). Five randomized clinical trials involving 3,028 patients were included: FOCUS and Pazdera were the only ones to analyze both scores, while one RCT exclusively evaluated the MIDAS score and two exclusively the HIT-6 score. In studies evaluating MIDAS, the relative improvement attributed to fremanezumab was not statistically significant after subtracting the effects observed in the control group (mean difference), being -0.27 (95% CI - 4.29 to 3.74; fremanezumab n = 806 vs."

HEOR • CNS Disorders • Migraine

Sustained response and clinical impact of anti-CGRP treatment in migraine patients: a retrospective observational study (IHC 2025) - "At 12 months, 60% and 66% of patients in the first and second cycles, respectively, reported reduced headache impact (HIT-6 <55). Conclusion The second fremanezumab treatment cycle demonstrated additional benefits during the initial 6 months, with sustained and comparable efficacy at 12 months, supporting the value of reinitiation in previously responsive patients"

Late-breaking abstract • Observational data • Retrospective data • CNS Disorders • Migraine

Four- year outcome on Fremanezumab therapy for Chronic Migraine prophylaxis; real-world data from Hull (UK) migraine clinic. (IHC 2025) - "Patients failed an average of 6 (range 5-11) treatments with 91% failing onabotulinumtoxinA. 20 stopped responding (resistant). Yearly summary of Fremanezumab outcome TIME N (F,M) Remission N(F,M) Resistant N(M,F) Relapse N (F,M) Continue 1 243 (187,56) 18 (15,3) 0 15(12,3) 240 (184,56) 2 240 (184,56) 33 (25,8) 21 (15,6) 10 (7,3) 195 (151,45) 3 196 (151,45) 19 (15,4) 17 (12,5) 0 160 (a24,36) 4 160 (124,36) 10 (7,3) 20 (14,6) 3 (3,0) 133 (106,27) 5 133 (106,27) Conclusion At year 5 only 21% were able to stop while 23.8% stopped responding after an initial response."

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

TRPM3 Channel Activation Triggers CGRP Release and Vasodilation in Trigeminal and Meningeal Tissues of Male and Female Rats: Implications for Migraine Pathophysiology (IHC 2025) - "A TRPM3 antagonist (BHV-2100) has recently advanced to phase II clinical trials for migraine treatment...Myograph studies on isolated middle cerebral arteries (MCA) were conducted to evaluate vasomotor responses to CIM0216, isosakuranetin, and fremanezumab, a monoclonal antibody targeting CGRP...TRPM3-induced vasodilation appears independent of CGRP, pointing to alternative mechanisms. These findings highlight a possible role for TRPM3 in migraine pathophysiology and support further investigation."

Preclinical • CNS Disorders • Migraine • TRPM3

Tolerability of Switch from Erenumab to Fremanezumab in Adults with Chronic Migraine. (IHC 2025) - "These findings highlight the clinical benefits of adjusting therapies based on patient tolerability. Further research is needed to assess the efficacy of switching between these treatments."

Clinical • CNS Disorders • Migraine

Real-world evidence of monoclonal antibodies for migraine treatment in Argentina: a retrospective analysis (IHC 2025) - "We reviewed electronic medical records of patients evaluated with migraine diagnosis who received Erenumab (ERE) or Fremanezumab (FRE) as preventive treatment between July 2019 and April 2025. Of note, most health insurance in Argentina do not cover these treatments. Our local data should reinforce the justification for expanding the use of specific migraine preventive treatments and increasing awareness among healthcare professionals and health insurance system."

HEOR • Real-world • Real-world evidence • Retrospective data • CNS Disorders • Migraine

Reduction of local adverse effects with slower infusion of fremanezumab – a case report (IHC 2025) - "Results A 34-year-old female with chronic migraine was refractory to four preventive treatments, including topiramate and botulinum toxin, both used at full therapeutic doses. Conclusion This case illustrates a worsening local reaction to fremanezumab with standard injections, and its resolution following a slower injection technique. Slowing the injection rate may improve tolerability in some patients and offers a simple, low-cost strategy to manage local adverse reactions."

Adverse events • Case report • Clinical • CNS Disorders • Migraine

Assessing real-world outcomes of fremanezumab: a retrospective, panel-based physician chart review study in Australia, Brazil, and Israel (IHC 2025) - "From 6 months pre- to post-index, outpatient office-based visits decreased significantly across all countries (all p < 0.05), and urgent care center/emergency room visits decreased significantly in AUS and BR (both p < 0.05). Conclusion These findings demonstrate the effectiveness of fremanezumab treatment across the three countries studied, with patients reporting improvements in MMD, MHD, MIDAS, and HIT-6 at Month 3 and HCRU at Month 6 post-initiation."

Real-world • Real-world evidence • Retrospective data • Review • CNS Disorders • Migraine

Efficacy outcomes from a Phase 3, randomized, double-blind, placebo-controlled study of fremanezumab for the preventive treatment of migraine in Chinese adults (IHC 2025) - "Conclusion All primary and secondary endpoints were met according to prespecified hierarchical analysis, with comparable results to fremanezumab studies in diverse populations, including different ethnicities. These results support the use of fremanezumab for migraine prevention in Chinese adults with migraine."

Clinical • P3 data • CNS Disorders • Migraine

Comparative Efficacy of Anti-CGRP Monoclonal Antibodies in the Preventive Treatment of Chronic Migraine: A Bayesian Network Meta-Analysis (IHC 2025) - "Galcanezumab 120 mg showed the highest response rate (RR: 1.993; 95% CrI: 1.489 to 2.809), followed by Fremanezumab 675/225 mg monthly (RR: 1.889; 95% CrI: 1.391 to 2.612) and Galcanezumab 240 mg (RR: 1.870; 95% CrI: 1.325 to 2.691). Although modest differences, Galcanezumab 120 mg showed the highest response rate, while Eptinezumab 300 mg led to the greatest reduction in migraine days. However, further studies are still needed to directly compare the efficacy of these drugs."

Retrospective data • CNS Disorders • Migraine

Trends in triptan, CGRP monoclonal antibody and gepant prescription rates in a large healthcare system in Boston, MA, USA from 2018-2024 (IHC 2025) - "Objective This study aims to describe triptan and CGRP inhibitor prescription rates by patient demographics in the Mass General Brigham Health System from 2018-2024 Methods We used electronic health record data from the Mass General Brigham Research Data Registry (RPDR) to identify patients 18 years or older with a migraine diagnosis (ICD-10 G43) and prescribed a triptan, CGRP monoclonal antibody (erenumab, galcanezumab, fremanezumab, eptinezumab) or gepant (ubrogepant, rimegepant, or atogepant) from May 1, 2018 and November 1, 2024. Conclusion Overall, there was an increase in the prescription rates for triptans, gepants and CGRP mABs in each demographic group from 2018-2024, although disparities were noted. Future analyses will investigate whether medical comorbidities and access to specialty clinics influence prescription rates."

Migraine