By: Alisha Kuriakose, PharmD Candidate c/o 2022
Every ten seconds, someone in the United States (U.S.) goes to the emergency room with complaints of head pain, many of which can be attributed to migraines. A migraine is a neurological condition characterized by intense and debilitating headaches. Those suffering from migraines may have experiences including nausea, vomiting, difficulty speaking, numbness or tingling and sensitivity to light (photophobia) and sound (phonophobia).1 In nearly one in four homes in the U.S., someone suffering from this condition. Women are three times more likely to experience it than men. Migraines can be hereditary and affect all ages, although they are most experienced in those between the ages of 18 and 44. Attacks can last for hours to days, and are oftentimes so severe that they interfere with activities of daily living. Hormonal changes in women such as the fluctuations in estrogen before or during pregnancy, menstrual periods and menopause or medications affecting hormones like oral contraceptives and hormone replacement therapy can worsen migraines. Other triggers for migraines include alcohol, caffeine, stress, weather and pressure changes, lack of sleep, bright lights, loud noises, and strong smells.1
On February 21st, 2020, the Food and Drug Administration (FDA) approved Lundbeck’s eptinezumab-jjmr (Vyepti™) for prophylactic treatment of migraine in adults. Eptinezumab-jjmr is the first and only intravenous infusion for preventative treatment of migraines. The humanized monoclonal antibody blocks the calcitonin gene-related peptide receptor by binding to its ligand.2 The Denmark based manufacturer recommends taking eptinezumab-jjmr in doses of 100 mg every three months, although some patients find that taking doses of 300 mg is also efficacious. Eptinezumab-jjmr is now marketed as its approved 100mg and 300 mg doses. The safety and efficacy of this drug was proven in randomized controlled clinical trials named Promise-1, which tested episodic migraine, and Promise-2, which tested chronic migraine. Trials took place at 212 sites in the U.S., Georgia, Russia, Ukraine, and the European Union. Studies were phase 3 clinical trials and compared the drug in question to a placebo with the primary endpoint of finding a decrease in mean monthly migraine days (MMD) over months 1-3.3 Positive effects were observed as early as one day after patients received the infusion. Participants could use concurrent acute migraine/headache medication during the trials, which may have contributed to some of the positive effects that were observed. Promise-1 defined episodic migraines as having between 4 and 14 headaches a month, of which at least 4 were migraine days. Promise-2 defined chronic migraine as having headaches for at least 15 to 26 days a month, 8 of which were considered migraine days. In both studies, patients were randomly given 100 mg, 300 mg, or the placebo. Changes from baseline in MMD were measured. Six hundred and sixty-five patients participated in Promise-1, 222 of whom received placebo, 221 patients received 100 mg eptinezumab-jjmr and the remaining were put into the 300 mg eptinezumab-jjmr group. The infusion was given to the patients 4 times over the course of 12 months. It was found that the, “mean migraine frequency at baseline was approximately 8.6 migraine days per month and was similar across treatment groups. Mean change from baseline in MMD with eptinezumab-jjmr compared with placebo months 1-3: -3.9 days for 100 mg (p=0.018), -4.3 days for 300 mg (p<0.001), and -3.2 days for placebo”.4 The decrease in mean migraine frequency from baseline demonstrates that this group experienced less migraines after being introduced to eptinezumab-jjmr.
Practice-2 had 1,072 participants who were randomly divided into a placebo group of 366, 100 mg Vyepti receiving group of 356 patients and the remaining 350 were placed in the 300 mg receiving eptinezumab-jjmr group. Treatment was given every 3 months for 6 months. This trial had a baseline mean migraine frequency of approximately 16.1 migraine days per month. From the trial, it was concluded that, the mean change in frequency of migraines from baseline in these patients in comparison to placebo were 1.3 -7.7 days for those taking 100 mg (p<0.001), -8.2 days for patients receiving 300 mg (p<0.001), and -5.6 days for the group taking placebo. Those who had a 50 percent reduction or greater during months 1 and 3 compared to placebo were observed as follows for each cohort—57.6 percent for the 100 mg group (p<0.001), 61.4 percent for patients receiving 300 mg (p<0.001), and 39.3 percent for those receiving placebo. Data for those who showed a 75 percent or more reduction in monthly migraine days between months 1 and 3 was as follows—26.7 percent for patients receiving 100 mg (p<0.001), 33.1 percent for patients receiving 300 mg (p<0.001), and 15 percent for patients receiving placebo.5
From both trials it can be concluded that eptinezumab-jjmr works similarly regardless of sex. Differences in how eptinezumab-jjmr worked among races could not be determined as most of the participants were white (1471 out of 1539 participants). The effects of eptinezumab-jjmr were similar in all tested age groups (patients ranged from 18-71). The number of patients older than 65 years was insufficient to determine if the medication worked differently in geriatric populations.4 Although no tests were explicitly performed to assess eptinezumab-jjmr’s effects on hepatic and renal function, pharmacokinetic impairment is not expected.
Two thousand and seventy-six patients were used to assess safety parameters, all patients received at least one dose of eptinezumab-jjmr. In these studies, common side effects were adverse effects that were observed in 2 percent or more of participants taking eptinezumab-jjmr or placebo. Side effects of eptinezumab-jjmr include serious allergic reactions such as swelling of face, tongue or throat, hives, trouble breathing, facial redness and rash.6 One point nine percent of participants discontinued the trial due to adverse effects, the most common being nasopharyngitis and hypersensitivity.
- Migraine without aura – ICHD-3 The International Classification of Headache Disorders 3rd edition. ICHD. https://ichd-3.org/1-migraine/1-1-migraine-without-aura/. Published April 19, 2019. Accessed April 3, 2020.
- Eptinezumab-jjmr (VYEPTI™) Approved By FDA for Migraine Prevention. American Headache Society. https://americanheadachesociety.org/news/eptinezumab-vyepti-approved-by-fda/. Published February 22, 1970. Accessed April 3, 2020.
- Center for Drug Evaluation and Research. Drug Trials Snapshots: VYEPTI. U.S. Food and Drug Administration. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-vyepti. Accessed April 3, 2020.accessdata.fda.gov. https://www.accessdata.fda.gov/. Accessed April 3, 2020.
- FDA approves Lundbeck’s Vyepti™ (eptinezumab-jjmr) – the first and only intravenous preventive treatment for migraine. H. Lundbeck A/S. https://investor.lundbeck.com/news-releases/news-release-details/fda-approves-lundbecks-vyeptitm-eptinezumab-jjmr-first-and-only. Accessed April 3, 2020.
- NOW APPROVED FOR MIGRAINE PREVENTION. Vyepti HCP. https://www.vyeptihcp.com/. Accessed April 3, 2020.