Introduction: The burden of migraines and new biologics
Migraines are a major global health issue, affecting an estimated 1.04 billion people worldwide and contributing to 45.1 million years lived with disability (YLDs). According to the Global Burden of Disease survey, migraine has steadily risen in impact over the years, ranking 19th in 2000, sixth in 2013, and second in 2016 in terms of YLDs.
It is especially disabling for people aged 15 to 49. This shows that migraines don’t just cause pain, they have a massive social and economic impact globally, affecting productivity, quality of life, and healthcare systems everywhere.1
Recent advances in migraine treatment have introduced a new class of drugs called CGRP inhibitors, which are biologics designed to prevent migraines by targeting specific molecules that trigger attacks. This is the first major innovation in migraine therapy since triptans were introduced around 20 years ago. 1
What is Ajovy (Fremanezumab)?
Fremanezumab, also called Ajovy®, is a medicine designed to prevent migraines in adults. It’s a special type of antibody made using advanced lab technology and works by blocking a molecule called CGRP, which is higher in people who get migraines. By targeting CGRP, fremanezumab helps reduce how often migraine attacks happen.
The medicine, approved by the FDA and the European Medicines Agency (EMA), is given as an injection under the skin, either 225 mg once a month or 675 mg every three months (split into three smaller injections). Each injection is done in the belly, thigh, or upper arm, and if you need multiple shots, they’re given in slightly different spots. Studies have shown that fremanezumab is effective in preventing both episodic and chronic migraines, giving people a new option to manage this often disabling condition.2
Migraine Pathophysiology
Migraines happen when a specific system in the brain called the trigeminovascular system gets activated. This system releases a chemical called CGRP, which is a small protein found in nerves throughout the body and brain. During a migraine attack, CGRP is released and binds to its receptor, causing blood vessels in the brain to widen and triggering inflammation. This chain of events contributes to the pain and other symptoms of a migraine.
CGRP works by activating a series of signals inside cells, ultimately leading to the widening of blood vessels and increased sensitivity in the nerves. Studies have shown that CGRP levels rise during migraine attacks, and blocking its action can help prevent the pain. Essentially, CGRP acts like a messenger that tells blood vessels to expand and nerves to become more sensitive, which plays a key role in causing migraines.2
Mechanism of Action
Fremanezumab is a special type of medicine called a monoclonal antibody that helps prevent migraines by targeting a molecule called CGRP. It mostly works outside the brain, likely at areas called the trigeminal ganglion and meningeal nociceptors, which are part of the pathway that sends migraine pain signals to the brain.
Studies in animals show that fremanezumab can block certain pain fibers called Aδ neurons from sending these signals, which stops the chain reaction that would normally result in migraine symptoms. By interfering with CGRP signaling along this trigeminovascular pathway, fremanezumab helps prevent the pain and other symptoms of migraines before they start.2
Ajovy vs. Other CGRP Inhibitors
Studies comparing the three main anti-CGRP migraine treatments, Ajovy (galcanezumab), Aimovig (erenumab), and Emgality (fremanezumab), show that all three are effective at reducing migraine frequency, intensity, and the need for other migraine medications.3
Over a year of treatment, a study of 160 patients found no significant differences between the three drugs in how many migraine days patients had per month, how intense their headaches were, or how much symptomatic medication they used. Even when the medications were paused for a month and then restarted, all three continued to provide similar benefits overall.
However, fremanezumab showed a better response at the 12-month mark for high-frequency episodic migraine patients. Overall, patients can expect meaningful migraine relief from any of the three anti-CGRP treatments.3
Clinical Trial Evidence
In the HALO CM study, 1,121 people with chronic migraines tried a fremanezumab. 375 got it every three months, 375 got it every month, and 371 got a placebo. The results showed clear benefits: people taking fremanezumab felt better in all areas of migraine-related quality of life, rated their overall health higher, and said their condition had improved much more than those on placebo. They also did better at work, with less interference from migraines and less impairment while working.4
Beyond physical and work improvements, fremanezumab also helped patients emotionally. People reported feeling more in control, less frustrated, and generally more positive about their day-to-day life.4
Another study showed that Fremanezumab helped reduce monthly migraine days by 7.2 days for Chronic Migraine (CM) quarterly, 8.0 days for CM monthly, 5.2 days for Episodic Migraines (EM) quarterly, and 5.1 days for EM monthly. Headache days of at least moderate severity also dropped by 6.4 days for CM quarterly, 6.8 days for CM monthly, 4.4 days for EM quarterly, and 4.2 days for EM monthly. Reductions in the use of acute headache medications and headache-related disability were maintained over 12 months.5
In summary, both monthly and quarterly doses worked well, showing the drug can help people with chronic migraines feel healthier, live more comfortably, and be more productive.4
Safety Profile
Most people taking fremanezumab experienced some side effects, with 84% to 89% reporting them, though serious issues were rare. The most common problems were mild reactions at the injection site, like redness, rash, swelling, or itching. Only 3% to 5% of people stopped the treatment because of side effects, and serious side effects happened in 5% to 7% of patients, but most were not linked to the drug itself.5
Liver problems were uncommon, affecting about 2% of patients, and most were mild and went away on their own. No severe allergic reactions or anaphylaxis occurred. Overall, fremanezumab was generally well tolerated, with most side effects being mild or manageable. 5
Conclusion
Fremanezumab (Ajovy®) is a biologic medicine designed to prevent migraines by targeting a molecule called CGRP, which plays a key role in triggering migraine attacks. Clinical studies have shown that both monthly and quarterly dosing can significantly reduce the number of migraine days and days with moderate-to-severe headaches. In people with chronic and episodic migraines, fremanezumab improved quality of life, overall health, emotional well-being, and productivity at work. Most patients experienced mild injection-site reactions, while serious side effects were rare. Liver issues and severe allergic reactions were uncommon, and overall the drug was well tolerated.
Note:
This content is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult your doctor or qualified healthcare provider before starting, changing, or stopping any medication. Individual responses to fremanezumab may vary, and only a healthcare professional can determine if it is appropriate for you.
Disclaimer:
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References:
- Rich SJ. Burden of migraine and impact of emerging therapies on managed care. Am J Manag Care. 2019;25(2 Suppl):S35-S39.
- Urits I, Clark G, An D, et al. An Evidence-Based Review of Fremanezumab for the Treatment of Migraine. Pain Ther. 2020;9(1):195-215. doi:10.1007/s40122-020-00159-3
- Tereshko Y, Dal Bello S, Pez S, et al. Comparative Study of the Efficacy of Anti-CGRP mAbs on Migraineurs: Analysis of the First Year of Therapy, 1-Month Suspension Period, and Reprisal. J Clin Med. 2023;12(23):7329. Published 2023 Nov 26. doi:10.3390/jcm12237329
- Lipton RB, Cohen JM, Gandhi SK, Yang R, Yeung PP, Buse DC. Effect of fremanezumab on quality of life and productivity in patients with chronic migraine. Neurology. 2020;95(7):e878-e888. doi:10.1212/WNL.0000000000010000
- Goadsby PJ, Silberstein SD, Yeung PP, et al. Long-term safety, tolerability, and efficacy of fremanezumab in migraine: A randomized study. Neurology. 2020;95(18):e2487-e2499. doi:10.1212/WNL.0000000000010600
