Emgality: Uses, Dosage & Side Effects

What Is Emgality and What Is It Used For?

Emgality contains the active substance galcanezumab, a humanized immunoglobulin G4 (IgG4) monoclonal antibody produced using recombinant DNA technology in Chinese hamster ovary (CHO) cells. As a monoclonal antibody, Emgality is a type of highly specialized protein engineered to recognize and bind to one specific molecular target in the body. In the case of Emgality, that target is calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide that has been identified as a central player in the pathophysiology of migraine.

CGRP is one of the most abundant neuropeptides in the human nervous system. It is expressed at high levels in the trigeminal ganglion and in perivascular nerve fibers that surround cerebral and meningeal blood vessels. During a migraine attack, CGRP is released in large quantities from trigeminal sensory neurons, triggering a cascade of pathological events: vasodilation of intracranial blood vessels, neurogenic inflammation in the meninges, sensitization of pain-processing neurons in the trigeminal nucleus caudalis, and transmission of pain signals to higher brain centers. Studies have consistently demonstrated elevated CGRP levels in the jugular venous blood of patients during acute migraine attacks, and intravenous infusion of CGRP in susceptible individuals has been shown to provoke migraine-like headaches, confirming its pivotal role in migraine pathogenesis.

Galcanezumab works by selectively binding to the CGRP ligand with high affinity, preventing it from activating its receptor. By neutralizing CGRP before it can initiate the downstream signaling cascade, galcanezumab effectively reduces the frequency and severity of migraine attacks, decreases headache-related disability, and lowers the need for acute rescue medications such as triptans and analgesics. Unlike small-molecule CGRP receptor antagonists (gepants), galcanezumab binds directly to the CGRP peptide itself rather than to its receptor. The antibody does not cross the blood-brain barrier in significant amounts; rather, it is thought to exert its preventive effects primarily in the peripheral trigeminovascular system, where CGRP-mediated signaling plays a crucial role in migraine initiation.

Emgality is indicated for the preventive treatment of migraine in adults who experience at least 4 migraine days per month. This includes patients with both episodic migraine (fewer than 15 headache days per month) and chronic migraine (15 or more headache days per month, of which at least 8 are migraine days). The clinical development program for Emgality included three pivotal phase III clinical trials:

• EVOLVE-1: A randomized, double-blind, placebo-controlled trial enrolling 858 adults with episodic migraine (4–14 migraine headache days per month). Over the 6-month treatment period, patients treated with galcanezumab 120 mg monthly (after a 240 mg loading dose) experienced a mean reduction of 4.7 monthly migraine headache days compared with 2.8 days for placebo, a statistically significant difference. The 50% responder rate (patients achieving at least a 50% reduction in monthly migraine days) was 62.3% for galcanezumab versus 38.6% for placebo.
• EVOLVE-2: A similarly designed trial enrolling 915 adults with episodic migraine. Patients on galcanezumab 120 mg experienced a mean reduction of 4.3 monthly migraine days versus 2.3 for placebo. The 50% responder rate was 59.3% for galcanezumab versus 36.0% for placebo.
• REGAIN: A randomized, double-blind, placebo-controlled trial in 1,113 adults with chronic migraine (15 or more headache days per month). During the 3-month double-blind period, galcanezumab 120 mg reduced monthly migraine headache days by 4.8 compared with 2.7 for placebo. The 50% responder rate was 27.6% for galcanezumab versus 15.4% for placebo.

In all three pivotal trials, Emgality demonstrated statistically and clinically meaningful improvements in monthly migraine days starting from the first month of treatment, with benefits apparent as early as one week after the initial loading dose. Long-term open-label extension studies have demonstrated sustained efficacy over 12 months and beyond, with continued reductions in migraine frequency, headache-related disability (as measured by the Migraine Disability Assessment or MIDAS score), and use of acute migraine medications.

Emgality was first approved by the U.S. Food and Drug Administration (FDA) in September 2018 and by the European Medicines Agency (EMA) in November 2018. It is now approved in more than 40 countries worldwide. In addition to migraine prevention, the FDA approved galcanezumab for the treatment of episodic cluster headache in adults in June 2019, making it the first drug specifically approved for this indication. However, the EU approval is specifically for migraine prevention.

What Should You Know Before Taking Emgality?

Contraindications

Emgality is contraindicated in patients with known hypersensitivity to galcanezumab or to any of the excipients in the formulation. The excipients include L-histidine, L-histidine hydrochloride monohydrate, polysorbate 80, sodium chloride, and water for injections. Before starting treatment, your healthcare provider should review your complete medical history and known allergies. If you have experienced an allergic reaction to another monoclonal antibody or biologic therapy, discuss this with your doctor, as cross-reactivity may occur in rare cases.

Emgality contains less than 1 mmol sodium (23 mg) per 120 mg dose and is therefore considered essentially sodium-free. This is relevant for patients on sodium-restricted diets, as there is no clinically meaningful sodium load associated with the injection.

Warnings and Precautions

Patients with serious cardiovascular disease should discuss the use of Emgality carefully with their healthcare provider. Clinical trials of galcanezumab excluded patients with serious cardiovascular conditions, including recent myocardial infarction, unstable angina, stroke or transient ischemic attack within the past 12 months, uncontrolled hypertension, or significant cardiac arrhythmias. Therefore, the safety and efficacy of Emgality in these populations has not been established. While CGRP plays a physiological role in cardiovascular regulation, including vasodilation and cardioprotection, the clinical significance of blocking CGRP with a monoclonal antibody in patients with cardiovascular disease remains uncertain and requires ongoing post-marketing surveillance.

Emgality is not recommended for children and adolescents under 18 years of age because it has not been studied in this age group. The pharmacokinetics, safety, and efficacy of galcanezumab in pediatric patients have not been established. Migraine is common in children and adolescents, but current treatment guidelines recommend other therapies for this population pending further clinical evidence.

Drug Interactions

No formal drug interaction studies have been conducted with galcanezumab. However, because galcanezumab is a humanized IgG4 monoclonal antibody, it is not metabolized by cytochrome P450 (CYP) enzymes and does not undergo hepatic metabolism in the same manner as small-molecule drugs. As a result, pharmacokinetic drug-drug interactions are not expected. The clearance of galcanezumab is not affected by concomitant use of other medications, including commonly used migraine treatments such as triptans, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or other preventive medications like topiramate, beta-blockers, and antidepressants.

Nevertheless, patients should always inform their healthcare provider about all medications they are currently taking, including prescription medications, over-the-counter drugs, and dietary supplements. Although no significant interactions have been identified, comprehensive medication review is standard clinical practice and helps ensure optimal treatment outcomes. If you are receiving treatment with another CGRP-targeting therapy (such as erenumab, fremanezumab, or a gepant like rimegepant or atogepant), discuss with your doctor whether combination therapy is appropriate, as there is limited clinical experience with concurrent use of multiple CGRP-pathway therapies.

Pregnancy and Breastfeeding

Women of childbearing potential are advised to use appropriate contraception and avoid becoming pregnant while being treated with Emgality. The effects of galcanezumab on human pregnancy are not known. Animal reproductive toxicology studies with galcanezumab in rats did not reveal any adverse effects on embryo-fetal development, fertility, or postnatal development at doses producing exposures significantly higher than those in humans. However, as these results may not be fully predictive of human outcomes, Emgality should not be used during pregnancy unless the potential benefit justifies the potential risk.

It is not known whether galcanezumab is excreted in human breast milk. Human IgG antibodies are known to be present in breast milk, particularly during the first few days after birth. Therefore, a risk to the breastfed infant cannot be excluded. A clinical decision must be made regarding whether to discontinue breastfeeding or to discontinue Emgality, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother. If you are breastfeeding or planning to breastfeed, discuss this with your doctor before starting Emgality.

Driving and Using Machines

Galcanezumab may have a minor influence on the ability to drive and use machines. Some patients have reported dizziness as a side effect of Emgality. If you experience dizziness after injection, you should avoid driving or operating machinery until the symptoms resolve. In clinical trials, the incidence of dizziness was low and generally mild, but individual responses may vary.

How Does Emgality Interact with Other Drugs?

Because galcanezumab is a monoclonal antibody that is catabolized (broken down) into amino acids through endogenous protein degradation pathways, it does not interact with the cytochrome P450 enzyme system or other drug-metabolizing enzymes. This mechanism of elimination is fundamentally different from that of small-molecule drugs and effectively eliminates the risk of pharmacokinetic drug-drug interactions. No formal drug interaction studies have been required by regulatory authorities because the pharmacological class and molecular properties of monoclonal antibodies make such interactions extremely unlikely.

In clinical trials, galcanezumab was administered concurrently with a wide range of medications commonly used by migraine patients, including acute treatments (triptans, ergotamine, NSAIDs, acetaminophen, opioids, antiemetics) and preventive treatments (beta-blockers, calcium channel blockers, anticonvulsants, antidepressants). No evidence of clinically significant pharmacokinetic or pharmacodynamic interactions was observed with any of these medication classes.

Although Emgality has a clean drug interaction profile, you should always inform your healthcare provider about all medications, supplements, and herbal products you use. This is particularly important if you are being considered for treatment with another medication that targets the CGRP pathway, such as erenumab (Aimovig), fremanezumab (AJOVY), or a CGRP receptor antagonist (gepant) such as rimegepant (Nurtec ODT) or atogepant (Qulipta). There is limited clinical experience with combining multiple CGRP-targeting therapies, and the potential for additive effects on CGRP signaling should be discussed with your physician.

What Is the Correct Dosage of Emgality?

Emgality should always be used exactly as prescribed by your healthcare provider. The pre-filled pen is designed for single use only and contains one dose of 120 mg galcanezumab in 1 mL of solution. Do not shake the pen. Before the first use, your doctor or nurse should demonstrate the proper injection technique. You may self-inject Emgality at home once you have been adequately trained, or a caregiver may administer the injection after receiving proper instruction.

Adults – Migraine Prevention

Injection Sites

Emgality should be injected subcutaneously (under the skin) into one of the following body areas: the abdomen (at least 5 cm away from the navel), the front of the thigh, the back of the upper arm (if administered by a caregiver), or the buttocks (if administered by a caregiver). Rotate injection sites with each dose and do not inject into the exact same spot each time. Do not inject into areas where the skin is tender, bruised, red, or hard.

Children and Adolescents

Emgality is not recommended for use in patients under 18 years of age, as safety and efficacy have not been established in this population. No pediatric clinical trials have been completed for galcanezumab. If you are the parent or guardian of a young person with migraine, consult your healthcare provider about appropriate treatment options.

Elderly Patients

No dose adjustment is necessary in elderly patients. Clinical trials of galcanezumab included patients up to 65 years of age, and no overall differences in safety or efficacy were observed compared with younger adults. However, as with all medications, individual clinical response should be monitored, and the benefits and risks of treatment should be discussed with the healthcare provider.

Missed Dose

If you miss a dose of Emgality, inject the missed dose as soon as you remember, and then continue with your next monthly dose from the new date. Do not take a double dose to make up for a forgotten injection. If you are uncertain about when to administer the next dose, contact your healthcare provider or pharmacist for guidance.

Overdose

If you have injected too much Emgality – for example, if you injected two doses in the same month after already receiving the loading dose of 240 mg, or if someone else has accidentally used your Emgality – contact your healthcare provider immediately. In clinical trials, doses up to 300 mg as a single subcutaneous injection were evaluated without evidence of dose-limiting toxicity. However, any suspected overdose should be reported to your doctor, who will provide guidance on monitoring and management.

What Are the Side Effects of Emgality?

Like all medicines, Emgality can cause side effects, although not everybody gets them. The overall safety profile of galcanezumab has been characterized in clinical trials involving more than 3,000 patients treated with galcanezumab for up to 12 months. The majority of side effects reported were mild to moderate in intensity, and the rate of treatment discontinuation due to adverse events was low (approximately 4% in the galcanezumab groups compared with 3% in placebo groups).

Injection site reactions are the most frequently reported side effects and are characteristic of subcutaneous administration of monoclonal antibodies. In clinical trials, injection site pain was reported by approximately 18% of patients receiving galcanezumab compared with 13% receiving placebo. Other injection site reactions (redness, itching, bruising, and swelling) were each reported in 5–10% of patients. These reactions are generally mild, do not require treatment, and typically resolve within hours to a few days.

Constipation was reported by approximately 4.5% of galcanezumab-treated patients compared with 2.5% of placebo-treated patients. This is consistent with the role of CGRP in gastrointestinal motility, as CGRP receptors are expressed throughout the enteric nervous system and CGRP is involved in the regulation of intestinal peristalsis. If you experience persistent or severe constipation, inform your healthcare provider.

Anti-drug antibodies (ADAs) developed in a proportion of galcanezumab-treated patients during clinical trials (approximately 12.4% during 12 months of treatment), with a small subset developing neutralizing antibodies. However, the development of ADAs did not appear to have a clinically meaningful impact on the pharmacokinetics, efficacy, or safety profile of galcanezumab. Post-marketing surveillance continues to monitor for any long-term immunogenicity concerns.

How Should You Store Emgality?

Proper storage of Emgality is essential to maintain the stability and efficacy of the medication. Keep this medicine out of the sight and reach of children. Do not use Emgality after the expiry date printed on the label and carton (after “EXP”). The expiry date refers to the last day of the stated month.

Emgality should be stored in the refrigerator at 2 °C to 8 °C (36 °F to 46 °F). Do not freeze the pre-filled pen. If the pen has been frozen, it must be discarded even if it has thawed, as freezing may damage the protein structure of the monoclonal antibody and affect its efficacy and safety. Keep the pens in their original carton to protect from light.

For convenience, Emgality may be taken out of the refrigerator and stored at room temperature (up to 30 °C / 86 °F) for a single period of up to 7 days. If the pre-filled pen has been stored at higher temperatures or for a longer period, it must be discarded. Once removed from the refrigerator and stored at room temperature, do not return the pen to the refrigerator. Before injection, allow the pen to reach room temperature by leaving it out for at least 30 minutes. Do not warm the pen using a microwave, hot water, or direct sunlight.

Before use, visually inspect the pre-filled pen. The solution should be clear and may be colorless to slightly yellow. Do not use the pen if it appears damaged, or if the solution is cloudy, discolored, or contains visible particles. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer needed. These measures help to protect the environment.

What Does Emgality Contain?

The active substance is galcanezumab, a humanized IgG4 monoclonal antibody. Each pre-filled pen contains 120 mg of galcanezumab in 1 mL of solution for injection. The antibody is produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells and undergoes extensive purification to ensure pharmaceutical-grade purity and consistency.

Emgality is supplied as a clear solution for injection in a clear glass syringe enclosed within a single-dose, disposable pre-filled pen. The color of the solution may vary from colorless to slightly yellow; both are normal and acceptable. Available pack sizes include 1, 2, or 3 pre-filled pens per carton. Not all pack sizes may be marketed in every country.

The marketing authorization holder for Emgality is Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands. Emgality is manufactured by Eli Lilly Italia S.p.A., Via Gramsci 731/733, 50019 Sesto Fiorentino (FI), Italy. For further information, the European public assessment report (EPAR) is available on the European Medicines Agency website.