FDA Approves First IV Treatment for Migraine Prevention

February 24, 2020

Eptinezumab-jjmr (Vyepti, Lundbeck) decreased mean monthly migraine days in adult patients in 2 phase 3 clinical trials.

Officials with the FDA have approved eptinezumab-jjmr (Vyepti, Lundbeck), the first intravenous (IV) treatment for the prevention of migraine in adults,  according to a press release.

Eptinezumab-jjmr is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor. The recommended dose is 100 mg every 3 months, but some patients may benefit from a 300-mg dose.

The approval is based on results from 2 phase 3 clinical trials: the PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine. In both studies, patients recieved either a placebo, eptinezumab-jjmr 100 mg, or eptinezumab-jjmr 300 mg. The primary endpoint was the change from baseline in mean monthly migraine day (MMD) over months 1 to 3. Patients were allowed to use concurrent acute migraine or headache medication, including migraine-specific medications, during the study.

Overall, the clinical trials demonstrated a treatment benefit over placebo for both doses of eptinezumab-jjmr as early as day 1 post-infusion. Additionally, the percentage of patients experiencing a migraine was lower for eptinezumab-jjmr than with placebo for most of the first 7 days. Among 2076 patients who received at least 1 dose of eptinezumab-jjmr, the most common adverse reactions were nasopharyngitis and hypersensitivity. In both trials, 1.9% of patients treated with eptinezumab-jjmr discontinued due to adverse reactions.

PROMISE-1 included a total of 665 patients who were randomized to 1 of the 3 treatment groups every 3 months for a 12-month period.

The results showed:

  • 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 to 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.

  • Percent responders with at least 50% reduction in MMD in months 1 to 3 compared with placebo: 49.8% for 100 mg (nominal statistical significance p=0.009), 56.3% for 300 mg (p<0.001), and 37.4% for placebo.

  • Percent responders with at least 75% in MMD in months 1 to 3: 22.2% for 100 mg (p=not statistically significant), 29.7% for 300 mg (p<0.001), and 16.2% for placebo.

  • Greater percentage of placebo-treated patients had migraine on most days during the first 7 days of treatment compared with eptinezumab-jjmr-treated patients.

 In PROMISE-2, a total of 1072 patents were randomized to receive a placebo, 100-mg eptinezumab-jjmr, or 300-mg eptinezumab-jjmr every 3 months for 6 months. According to the data:

  • Mean migraine frequency at baseline was approximately 16.1 migraine days per month and was similar across treatment groups.

  • Mean change from baseline in MMD compared with placebo months 1 to 3: 7.7 days for 100 mg (p<0.001), -8.2 days for 300 mg (p<0.001), and -5.6 days for placebo.

  • Percent responders with at least 50% reduction in MMD in months 1 to 3 compared with placebo: 57.6% for 100 mg (p<0.001), 33.1% for 300 mg (p<0.001), and 15% for placebo.

  • Greater percentage of placebo-treated patients had migraine on each individual day during the first 7 days of treatment compared with eptinezumab-jjmr-treated patients.

“The PROMISE-2 data showed that many patients can achieve reduction in migraine days of at least 75% and experience a sustained migraine improvement through 6 months, which is clinically meaningful to both physicians and patients,” Dr Peter Goadsby, a professor of neurology at King’s College, London and the University of California, San Francisco, said in a statement. “Vyepti is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease.”

Eptinezumab-jjmr will be available in April 2020, according to Lundbeck.

 

References:

1. FDA approves Lundbeck’s VYEPTI (eptinezumab-jjmr)–the first and only intravenous preventive treatment for migraine [news release]. Lundbeck’s website. https://www.newsroom.lundbeckus.com/news-release/2020/fda-approves-lundbecks-vyepti-eptinezumab-jjmr-for-migraine. Accessed February 24, 2020.