Emgality (galcanezumab-gnlm) / Eli Lilly, Daiichi Sankyo, AffaMed Therap, Organon - LARVOL DELTA

Increased infection risk in patients on preventive CGRP-targeting therapies- a meta-analysis and clinical effect assessment. (PubMed, J Headache Pain) - "CGRP has multiple and often potentially opposing effects on the immune system. In effect, preventive CGRP pathway antagonists (especially eptinezumab and galcanezumab) possibly only mildly increase the risk of infections. However, it is unlikely to affect most migraine patients considering relatively high NNH, low effect size and few infectious SAEs reported so far. The result of CGRP-targeting therapies potentially depends on the type of pathogen and patient's immune status. Consequently, in immunocompromised patients or at public health levels the increased infection risk may have more pronounced effect."

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

Identifying signals of disproportionate reporting for calcitonin gene-related peptide inhibitors: real-world evidence from the FDA adverse event reporting system. (PubMed, Expert Opin Drug Saf) - "Galcanezumab showed strong signals for underdose (ROR 47.4; 95% CI 43.79-51.3), alopecia (5.72; 5.09-6.43), and constipation (6.01; 5.35-6.75), while fremanezumab exhibited notable associations with alopecia (6.9; 5.72-8.33) and weight increased (6.34; 5.18-7.76). Among gepants, rimegepant was linked to somnolence (4.52; 3.57-5.73) and dizziness (3.73; 3.15-4.42) and atogepant showed a strong signal for therapy interruption (16.58; 12.86-21.38). This study highlights CGRP inhibitor-associated AEs, underscoring the need for clinical monitoring and risk identification. Early detection of AEs and SDRs can inform protective measures to enhance patient safety."

Adverse events • HEOR • Journal • Real-world evidence • Alopecia • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Migraine • Pain

Migraine treatment with CGRP monoclonal antibodies: patient evaluation of a mandatory treatment holiday in Belgium. (PubMed, Acta Neurol Belg) - "A rigid, mandatory treatment holiday of two to three months poses significant challenges for a substantial subset of patients, leading to rapid migraine deterioration and increased anxiety. The observed association between migraine deterioration and anxiety highlights the need for patient education strategies. Policy makers should consider these findings to develop more flexible, patient-centered treatment approaches that optimize outcomes."

Journal • CNS Disorders • Migraine • Mood Disorders • Pain • Psychiatry

Monthly Headaches and Severity in Patients on Galcanezumab or Traditional Preventive Migraine Medication: A 24-Month Claims and Electronic Health Records Study. (PubMed, Neurol Ther) - "In this exploration of multiple data sources and methodologies, changes in MHDs over 24 months were small in patients treated with galcanezumab or SOC. While real-world data from administrative claims and EHR provided insights, limitations such as small sample sizes for migraine severity data and challenges in extracting clinical outcomes underscore the need for further research."

Journal • CNS Disorders • Migraine • Pain • Preventive care

Predictors of Response to Treatment With Anti-calcitonin Gene-Related Peptide (CGRP) Antibodies in Real-World Patients With Episodic Migraine: A Two- and Four-Month Prospective Study. (PubMed, Cureus) - "Normal BMI was found to be significantly associated with a reduction in migraine frequency of >50%, whereas normal BMI, unilateral headache, and severe osmophobia were significantly associated with a mean MHD reduction. Further controlled studies with several other factors predicting response to anti-CGRP mAbs are warranted."

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

Successful Management of Wearing-off effect with Eptinezumab: Lessons from a case with Chronic Migraine Refractory to Two Subcutaneous CGRP Antibodies (PubMed, Rev Neurol) - "She failed to respond to multiple oral preventatives, botulinum toxin, and two CGRP antibodies (erenumab and galcanezumab). Conclusions CGRP antibodies can show a wearing-off effect, which should be identified in order to plan individualized treatment and avoid an incorrect interpretation as therapeutic failure. Our case also shows that patients with chronic migraine refractory to two antibodies can respond to a third CGRP antibody, in this case, intravenous eptinezumab."

Journal • CNS Disorders • Migraine • Pain

A National Cross-Sectional Survey on Real-World Experiences of Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibody Use in Adults with Migraine in Finland. (PubMed, Pain Ther) - "Patient experiences of using subcutaneous CGRP mAbs in Finland showed improvements in several migraine-related factors, supporting the potential for CGRP mAbs to improve the quality of life of adults with migraine."

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

Health care resource utilization and direct costs incurred over 12 months by patients with migraine initiating self-injectable calcitonin gene-related peptide monoclonal antibodies: A US real-world study. (PubMed, J Manag Care Spec Pharm) - "HCRU and direct cost differences observed at 12 months following initiation of self-injectable CGRP mAbs for migraine prevention were numerically similar across cohorts for patients treated with galcanezumab, fremanezumab, and erenumab. More work should be done to learn if these drugs perform differently with respect to other important factors not examined here."

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

Patient satisfaction with calcitonin gene-related peptide monoclonal antibodies in migraine: A multicenter prospective cohort study. (PubMed, Headache) - "Most patients were satisfied with CGRP mAbs' effectiveness, tolerability, and convenience in a real-world setting. Interestingly, increasing TS was associated with meaningful reductions in frequency, impact, and disability caused by migraine."

Journal • CNS Disorders • Migraine • Pain

The Effect of Galcanezumab-gnlm on Post-Traumatic, Migrainous Headaches (clinicaltrials.gov) - P4 | N=25 | Completed | Sponsor: Albany Medical College

New P4 trial • Migraine • Pain

CROATIAN GUIDELINES FOR SPECIFIC PREVENTIVE TREATMENT OF MIGRAINE WITH MONOCLONAL ANTIBODIES TARGETING CALCITONIN GENE-RELATED PEPTIDE (CGRP) (EPTINEZUMAB, FREMANEZUMAB, AND GALCANEZUMAB) OR THE CGRP RECEPTOR (ERENUMAB). (PubMed, Acta Clin Croat) - "These medications may be considered as first-line prophylactic therapy depending on the patient's history, concomitant diseases, and disease burden. Further real-world studies are needed to elucidate other aspects of their application."

Clinical guideline • Journal • Review • CNS Disorders • Inflammation • Migraine • Pain

Efficacy and continuability of 675 mg fremanezumab administration over 2 years. (PubMed, J Headache Pain) - "Fremanezumab 675 mg quarterly dose effectively reduces headache frequency over an extended period and may facilitate medication cessation in patients who experience substantial recovery."

Journal • Observational data • CNS Disorders • Dermatology • 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 (AAN 2025) - "Objective:Network meta-analysis (NMA) of atogepant (Ato) relative to rimegepant (Rime) and galcanezumab (Galc) after inclusion of the CHALLENGE-MIG trial for efficacy and safety outcomes in episodic migraine (EM) patients.Background:The NMA included 5 randomized, controlled trials for the preventive treatment of EM (ADVANCE [Ato 60 mg], BHV3000-305 [Rime 75 mg], EVOLVE-1, EVOLVE-2 [Galc 120 mg], and CHALLENGE-MIG [Rime 75 mg, Galc 120 mg]).Design/A fixed-effects model was chosen to compare the efficacy and safety of Ato versus Rime, Galc based on model fit statistics. Ato 60 mg demonstrated significant improvements in 3 of the 4 efficacy outcomes compared to Rime 75 mg and significantly increased odds of achieving ≥50% RR in MMD relative to Galc 120 mg. Other efficacy outcomes were not significantly different. Ato 60 mg demonstrated comparable all-cause d/c and TEAEs relative to Rime and Galc."

Retrospective data • CNS Disorders • Migraine • Pain

The Safety and Effectiveness of Dual Calcitonin Gene-Related Peptide (CGRP) Therapies for Migraine Treatment: A Focus on Small Molecule Antagonist and Ligand Monoclonal Combinations (AAN 2025) - "Our study aims to assess the effects of this dual-CGRP approach.Design/A retrospective matched cohort study was conducted at a neurological care center in Hawaii, analyzing 90 chronic migraine patients aged ≥18 years treated with CGRP inhibitors (L-mAbs: fremanezumab, galcanezumab, eptinezumab; SMAs: ubrogepant, rimegepant, atogepant; or a combination)...Variables included age, age at diagnosis, sex, onabotulinumtoxinA use, headache frequency, duration, severity, and associated symptoms before and three months post-treatment...Dual-CGRP regimens may provide improved effectiveness for controlling migraine symptoms by significantly reducing headache severity and aura symptoms without significant adverse events."

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

Galcanezumab Efficacy in Cluster Headache: A Systematic Review with Single-Arm Meta- Analysis (AAN 2025) - "The use of Galcanezumab for cluster headache can effectively reduce the frequency of attacks after treatment compared to baseline especially during the first weeks. However, the analysis of placebo-controlled studies showed no significant reduction. Further investigations are needed in subgroups of patients who are refractory to other treatments and with a larger sample size."

Clinical • Review • Pain

Treatment Patterns and Healthcare Resource Utilization by Gender and Migraine Frequency in Adult Patients Receiving Galcanezumab Versus Standard of Care Preventive Medications Over 24 months: A United States Retrospective Claims Study. (PubMed, Patient Prefer Adherence) - "Increases in HCRU associated with preventive migraine medication counts and migraine-related total and pharmacy costs were significantly higher in GMB versus SOC cohorts in all subgroups. While direct costs over 24 months were higher in patients initiating GMB for migraine prevention, better adherence and longer treatment duration with GMB regardless of gender or migraine type support the use of GMB compared with SOC."

HEOR • Journal • Retrospective data • CNS Disorders • Migraine • Pain • Preventive care

Real-World Lessons with Fremanezumab as the Third Available CGRP Monoclonal Antibody in a Third-Level Hospital: Focus on the Factors Predicting Response. (PubMed, J Clin Med) - "Totals of 17 and 26 patients had been treated at least with galcanezumab or erenumab. The main factors associated with a lack of response were almost daily/daily headaches and a disease duration > 6 years. Half of the patients who failed to respond to erenumab improved on fremanezumab, making it sensible to switch to a treatment with a different mechanism of action, but trying a third anti-CGRP treatment in patients with no response to both a receptor-targeted and a ligand-targeted CGRP antibody hardly seems justifiable from our experience."

Journal • Real-world evidence • CNS Disorders • Depression • Fibromyalgia • Migraine • Mood Disorders • Musculoskeletal Pain • Pain • Psychiatry • Rheumatology

Review: An Update on CGRP Monoclonal Antibodies for the Preventive Treatment of Episodic Migraine. (PubMed, Curr Pain Headache Rep) - "Erenumab (AMG334), fremanezumab (TEV48125), and galcanezumab (LY2951742) are monthly subcutaneous injections, while eptinezumab (ALD403) provides an intravenous infusion option. These investigations have built evidence for earlier access to CGRP treatment as they increase quality of life and reduce monthly migraine days while being better tolerated than non-specific migraine preventative therapies. These studies support the recent 2024 AHS consensus statement recommending CGRP monoclonal antibodies be considered as first-line preventive treatment in episodic migraine."

Journal • Review • CNS Disorders • Migraine • Pain

Peripherally acting anti-CGRP monoclonal antibodies attenuate cortical resting-state connectivity in migraine patients. (PubMed, Cephalalgia) - "These findings suggest that even a relatively short period of reduced nociceptive signals may be sufficient to initiate a cortical recovery process in which its resting hyperexcitable mode shifts to a less excitable state."

Journal • CNS Disorders • Migraine • Pain

Health Technology Assessment: Evaluation of 8 CGRP-Targeted Therapy Drugs for the Treatment of Migraine. (PubMed, Drug Des Devel Ther) - "The final assessment result scores from highest to lowest were rimegepant (84.5 points), erenumab (75.78 points), galcanezumab (74.02 points), fremanezumab (73.93 points), atogepant (72.64 points), eptinezumab (71.69 points), ubrogepant (70.37 points), zavegepant (56.44 points). Rimegepant, erenumab, fremanezumab, atogepant, galcanezumab, eptinezumab, ubrogepant can be entered into the medication list of medical institutions as strongly recommended drugs."

Journal • Review • CNS Disorders • Migraine • Pain

Organon Reports Results for the Fourth Quarter and Full Year Ended December 31, 2024 (GlobeNewswire) - "Biosimilars revenue increased 12% on both an as-reported and ex-FX basis for full year 2024, compared with the prior year, primarily driven by growth in Hadlima, following its U.S. launch in July 2023. Renflexis and Ontruzant declined 1% ex-FX and 9% ex-FX, respectively, as both products are in the mature phase of their product life cycles and face significant competitive pricing pressure. Established Brands revenue grew 2% both on an as-reported basis and ex-FX in the fourth quarter of 2024, primarily related to the revenue contribution of Emgality (galcanezumab-gnlm) and Vtama (tapinarof), which together more than offset the impact of the loss of exclusivity ('LOE') of Atozet (ezetimibe and atorvastatin) in key markets in Europe and in Japan."

Commercial • Ankylosing Spondylitis • Atherosclerosis • Atopic Dermatitis • Breast Cancer • Crohn's disease • Dyslipidemia • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Positive Breast Cancer • Migraine • Psoriasis • Psoriatic Arthritis • Rheumatoid Arthritis • Ulcerative Colitis

Disproportionality analysis of Raynaud's phenomenon associated with calcitonin gene-related peptide inhibitors using the Food and Drug Administration adverse event reporting system. (PubMed, Sci Rep) - "CGRP inhibitors demonstrated significant SDRs for Raynaud's phenomenon (ROR 19.12; 95% CI 15.44-23.69), with rimegepant, ubrogepant, and atogepant showing particularly strong signals. Intra-class analysis revealed a significant SDR only for galcanezumab (ROR 2.01; 95% CI 1.28-3.17). Inter-class analysis indicated significant SDRs for CGRP inhibitors compared to beta-blockers, anticonvulsants, and celecoxib, but not triptans. These findings underscore the importance of ongoing pharmacovigilance and further research to validate these associations and ensure patient safety."

Adverse events • Journal • Retrospective data • Cardiovascular • CNS Disorders • Migraine • Pain • Rheumatology

The effect of calcitonin gene-related peptide monoclonal antibodies on restless legs syndrome in patients with migraine. (PubMed, J Headache Pain) - "Our study revealed that 3-month CGRP mAb treatment significantly alleviated RLS symptoms, central sensitization and headache-related disability in patients with comorbid migraine and RLS."

Journal • CNS Disorders • Migraine • Movement Disorders • Pain • Restless Legs Syndrome • Sleep Disorder

Prevention of Episodic Migraine Headache Using Pharmacologic Treatments in Outpatient Settings: A Clinical Guideline From the American College of Physicians. (PubMed, Ann Intern Med) - "ACP evaluated the comparative effectiveness of the following interventions: angiotensin-converting enzyme inhibitors (lisinopril), angiotensin II-receptor blockers (candesartan and telmisartan), antiseizure medications (valproate and topiramate), β-blockers (metoprolol and propranolol), calcitonin gene-related peptide (CGRP) antagonist-gepants (atogepant or rimegepant), CGRP monoclonal antibodies (eptinezumab, erenumab, fremanezumab, or galcanezumab), selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors (fluoxetine and venlafaxine), and a tricyclic antidepressant (amitriptyline). All 3 ACP recommendations have conditional strength and low-certainty evidence. Clinical considerations provide additional context for physicians and other clinicians."

Clinical guideline • Journal • CNS Disorders • Epilepsy • Migraine • Pain

Switching between anti-cgrp monoclonal antibodies in migraine prophylaxis. (PubMed, Expert Rev Neurother) - "Switching between different anti-CGRP mAbs may be beneficial, at least for some patients, and should be considered when therapy with a first anti-CGRP mAb fails for any reason. Larger prospective studies, employing standardized protocols for switching or comparative effectiveness trials between mAbs, are anticipated to elucidate this issue further."

Journal • Review • CNS Disorders • Migraine • Pain