What is the dosing regimen and efficacy of Ajovy (fremanezumab) for preventive treatment of migraines in adults?

Ajovy (Fremanezumab) for Migraine Prevention

Dosing Regimen

Ajovy is administered subcutaneously at either 225 mg monthly OR 675 mg every 3 months (quarterly), with both regimens demonstrating equivalent efficacy for migraine prevention. 1

Administration Details

• Quarterly dosing: 675 mg administered as three consecutive subcutaneous injections of 225 mg each at baseline, then repeated every 3 months 1
• Monthly dosing: 225 mg administered as a single subcutaneous injection every month 1
• Injection sites: Abdomen, thigh, or upper arm (rotate sites, avoid tender/bruised areas) 1
• Preparation: Remove from refrigerator and allow to reach room temperature for 30 minutes before injection; do not use if at room temperature for ≥7 days 1
• Switching regimens: When switching between monthly and quarterly dosing, administer the first dose of the new regimen on the next scheduled date 1

Efficacy Data

Episodic Migraine (EM)

Fremanezumab reduces monthly migraine days by approximately 3-4 days in episodic migraine, with 38-41% of patients achieving ≥50% reduction in headache frequency. 2, 3

• Baseline: 8.9-9.2 monthly migraine days 2
• At 12 weeks: Reduced to 5.3 days (both monthly and quarterly dosing) 2
• At 6 months: Further reduced to 4.0-4.2 days 2
• Responder rates: 38% (quarterly) and 41% (monthly) achieved ≥50% reduction versus 18% with placebo (p<0.001) 3

Chronic Migraine (CM)

In chronic migraine, fremanezumab reduces monthly headache days by 4-5 days at 12 weeks, with sustained improvement reaching 7-8 day reduction by 12 months. 2, 3

• Baseline: 16.2-16.4 monthly headache days 2, 3
• At 12 weeks: Reduced to 11.4-11.9 days (4.3-4.6 day reduction versus 2.5 days with placebo, p<0.001) 2, 3
• At 6 months: Further reduced to 8.3-9.9 days 2
• At 12 months: Sustained reduction to 8.3-12.0 days depending on dosing regimen 4
• Responder rates: 38-41% achieved ≥50% reduction in headache days versus 18% with placebo (p<0.001) 3

Real-World Effectiveness

Real-world data from 165 patients demonstrates sustained efficacy over 12 months, with progressive improvement particularly notable in chronic migraine after 6 months of treatment. 4

• Episodic migraine: Baseline 8.1 days reduced to 4.6 days at 12 months 4
• Chronic migraine: Baseline 20.9 days reduced to 12.0 days at 12 months 4
• Treatment benefits enhanced after 6 months in chronic migraine patients 4

Guideline-Based Positioning

The 2025 American College of Physicians guidelines position fremanezumab as second-line monotherapy for episodic migraine prevention after failure of first-line agents (beta-blockers, topiramate, valproate, amitriptyline, or venlafaxine). 5, 6

Treatment Algorithm

1. First-line options: Metoprolol, propranolol, topiramate, valproate, amitriptyline, or venlafaxine 5
2. Second-line options: CGRP monoclonal antibodies (fremanezumab, erenumab, galcanezumab, eptinezumab) after documented failure or intolerance of first-line agents 5
3. Strong recommendation: The VA/DoD 2024 guideline upgraded fremanezumab to "strong for" recommendation based on demonstrated efficacy in reducing monthly migraine days and acute medication use 5

Additional Clinical Benefits

Beyond headache reduction, fremanezumab significantly decreases acute medication use, migraine-associated symptoms, and headache-related disability. 3, 7, 8

• Acute medication reduction: 1.3-1.4 fewer days of any acute headache medication use versus placebo (p<0.001) 8
• Migraine-specific medication reduction: 2.2 fewer days versus placebo (p<0.001) 8
• Associated symptoms: Significant reduction in nausea/vomiting, photophobia, and phonophobia 8
• Comorbid depression: Effective in patients with moderate-to-severe depression (PHQ-9 ≥10), with 40% achieving ≥50% headache reduction versus 13% with placebo (p<0.001) 7
• Headache Impact Test (HIT-6): Significant improvement in disability scores 7

Safety Profile

The most common adverse events are injection site reactions (pain 24%, induration 17%, erythema 16%), with severe adverse events occurring at rates similar to placebo (3.9% vs 3.7%). 1, 2

Key Safety Considerations

• Contraindication: Serious hypersensitivity to fremanezumab or excipients (including anaphylaxis and angioedema) 1
• Hypersensitivity reactions: Rash, pruritus, urticaria reported; most mild-to-moderate but some required discontinuation or corticosteroid treatment 1
• Hepatic function: Abnormalities occurred in 1% of fremanezumab patients versus <1% placebo 3
• No cardiovascular concerns: No changes in vital signs or ECG reported in clinical trials 2
• Pregnancy/lactation: Discuss risks with patients of childbearing potential 5

Treatment Duration and Response Assessment

Assess treatment efficacy after 3 months of therapy; patients showing inadequate response should be transitioned to alternative preventive treatments. 6

• Minimum trial period: 3 months before determining treatment failure 6
• Response definition: ≥30-50% reduction in monthly migraine days is considered clinically meaningful 6, 3
• Progressive benefit: Some patients, particularly those with chronic migraine, demonstrate enhanced benefit after 6 months of continuous treatment 4
• Failure of one CGRP antibody: Does not predict failure of other drug classes; consider alternative preventive mechanisms if fremanezumab fails 6

Important Clinical Caveats

• Medication overuse headache: Screen for and address medication overuse (≥10 days/month triptans, ≥15 days/month NSAIDs) as this reduces preventive treatment effectiveness 5, 6
• Cost considerations: CGRP monoclonal antibodies are significantly more expensive than first-line oral preventives; ensure documented failure of conventional therapies 6, 9
• Route of administration: Subcutaneous injection may be preferred over IV administration (eptinezumab) for patients preferring self-administration at home 5, 6
• Long-term safety: Post-marketing surveillance ongoing; long-term effects beyond 12 months require further study 2