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

AJOVY – global revenues of $168 million (+19% LC YoY). Reaffirming 2025 revenue outlook of $630 million - $640 million. (Teva Press Release)

Sales • Migraine

The clinical outcome of patients starting monoclonal antibodies anti-CGRP with concomitant migraine preventive treatments. (PubMed, Cephalalgia) - "The analysis was conducted on 555 patients who started galcanezumab (260; 46.8%), erenumab 140 mg (167; 30.0%) or fremanezumab (128; 23.1%). Overall, 13% of patients reported at least one adverse event.ConclusionsOur study confirms that concomitant SPTs at baseline do not influence the clinical outcome of CGRP mAbs after six months of treatment. A progressive withdrawal of SPTs during 12-month anti-CGRP therapy was observed, dissimilar among preventive classes, with persistence of SPTs at T12, mainly in patients with comorbid conditions."

Clinical data • Journal • Observational data • CNS Disorders • Migraine • Pain

The second interim analysis of Italian participants enrolled in the real-world, Pan-European, prospective, observational, Phase 4 PEARL study of fremanezumab effectiveness. (PubMed, Neurol Sci) - "Fremanezumab was effective and well tolerated in Italian clinical practice, with results in line with those previously reported for fremanezumab in a real-world setting."

Journal • Observational data • P4 data • Real-world evidence • CNS Disorders • Migraine • Pain

Migraine Medication Effects on Urinary Symptoms (clinicaltrials.gov) - P=N/A | N=200 | Enrolling by invitation | Sponsor: The Cleveland Clinic | Trial completion date: May 2026 ➔ Dec 2026 | Trial primary completion date: May 2025 ➔ May 2026

Trial completion date • Trial primary completion date • CNS Disorders • Interstitial Cystitis • Migraine • Musculoskeletal Pain • Overactive Bladder • Pain

Impact of anti-CGRP monoclonal antibodies on treatment satisfaction and quality of life in patients with resistant migraine: a retrospective real-world study. (PubMed, BMC Neurol) - "Patient satisfaction with anti-CGRP mAb therapy was high in this real-world study and correlated with effectiveness measured by the HIT-6 and significantly improved quality of life. Anti-CGRP mAbs are effective and safe for resistant migraine; they have a quick onset of action and provide lasting relief."

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

REAL-WORLD EVIDENCE ON INTRAVENOUS EPTINEZUMAB IN PATIENTS WITH EPISODIC MIGRAINE (WCN 2025) - "They reported in 71% (10/14) prior subcutaneous anti-CGRP mAb use (i.e., fremanezumab, galcanezumab, or erenumab). Our Belgian, real-world data showed that patients with episodic migraine with prior exposure to subcutaneous anti-CGRP mAbs had high overall satisfaction and tolerance after the switch to intravenuous eptinezumab."

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

INTERIM RESULTS FROM A POST-MARKETING SURVEILLANCE STUDY OF PATIENTS WITH MIGRAINE TREATED WITH FREMANEZUMAB IN KOREA (WCN 2025) - "Fremanezumab for migraine prevention was well tolerated in Korean adults in a real-life setting, with more favorable MMD reductions from baseline than reported in clinical trials."

Clinical • P4 data • CNS Disorders • Migraine • Pain

EFFICACY OF FREMANEZUMAB IN MIGRAINE PREVENTION (WCN 2025) - "FRM demonstrated sustained long-term efficacy and significant clinical benefits, including in patients with comorbidities like depression and medication overuse. Its innovative mechanism and favorable pharmacokinetics make it a promising option for migraine prevention."

Clinical • CNS Disorders • Depression • Migraine • Pain • Psychiatry

A SINGLE CENTER REAL-WORLD STUDY ON LONG-TERM EFFICACY AND TOLERABILITY OF FREMANEZUMAB IN MIGRAINE PATIENTS OVER 24 MONTHS (WCN 2025) - "Fremanezumab is effective and well-tolerated for long-term migraine prevention."

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

CORTICAL THICKNESS CHANGES IN MIGRAINE PATIENTS TREATED WITH ANTI-CGRP MONOCLONAL ANTIBODIES: A PROSPECTIVE AGE- AND SEX-MATCHED CONTROLLED STUDY (WCN 2025) - "Anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) are a novel therapy for migraine prevention, but their effects on cortical structures are poorly understood. In this prospective, age- and sex-matched controlled study, 30 migraine patients receiving either anti-CGRP mAbs (fremanezumab) (n=15) or oral preventive medications (n=15) underwent 3T MRI scans before and after treatment... Treatment response to anti-CGRP mAbs was associated with region-specific cortical thickness changes. These findings suggest that anti-CGRP mAbs may modulate migraine-related brain abnormalities in responders, providing insights into their central mechanisms of action beyond peripheral effects."

Clinical • CNS Disorders • Migraine • Pain

Patient Adherence and Long-Term Tolerability of Anti-calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibodies in Migraine Prevention: A Systematic Review. (PubMed, Cureus) - "Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs: erenumab, fremanezumab, galcanezumab, and eptinezumab) represent a targeted therapeutic advance, but long-term adherence and safety remain under investigation. Responder rates (≥50% reduction in monthly migraine days) improved from 44% at three months to 64% at 12 months, with network meta-analyses suggesting greater efficacy compared with topiramate and OnabotulinumtoxinA, though direct head-to-head RCTs remain lacking. Overall, anti-CGRP mAbs demonstrate favorable adherence, sustained tolerability, and comparative advantages over conventional therapies, but further research is needed to assess long-term safety beyond 12 months, cost-effectiveness, and use in special populations such as pregnancy."

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

A Study to Test if Fremanezumab is Effective in Preventing Migraine in Children and Adolescents (clinicaltrials.gov) - P3 | N=506 | Active, not recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D LLC | Completed ➔ Active, not recruiting | Trial completion date: Sep 2025 ➔ Dec 2025

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

Long-term real-world effectiveness and safety of fremanezumab in 1140 patients with migraine and at least 6 months of treatment: third interim analysis of the pan-European PEARL study. (PubMed, Neurol Sci) - "Findings from this third interim analysis of PEARL provide compelling evidence for the long-term effectiveness of fremanezumab in a large, real-world patient population. The results support the continued use of fremanezumab as a preventive strategy for migraine and underscore the value of integrating real-world evidence into migraine management."

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

Fremanezumab: Pediatric First Approval. (PubMed, Paediatr Drugs) - "In August 2025, it was approved in the USA for the preventive treatment of episodic migraine in pediatric patients aged 6-17 years who weigh 45 kg or more. This article summarizes the milestones in the development of fremanezumab leading to this pediatric first approval for migraine."

Journal • Review • CNS Disorders • Migraine • Pain • Pediatrics

Number Needed to Treat and Cost Per Responder Analysis of Anti-CGRP Monoclonal Antibodies for Migraine Prevention in Adults for Whom Prior Preventive Treatments have Failed. (PubMed, Adv Ther) - "These results show that, for most anti-CGRP mAbs, a low number of participants (< 10) with migraine need to be treated to achieve one person with a ≥ 50% or ≥ 75% reduction in MMDs over Weeks 1-12, with CPR ranging from £4647 (eptinezumab 100 mg) to £21,862 (fremanezumab 675 mg/q)."

Clinical • HEOR • Journal • CNS Disorders • 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 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