H. Lundbeck A/S recently announced that Vyepti (eptinezumab-jjmr) has been approved by the U.S. Food and Drug Administration (FDA) for the preventive treatment of migraine in adults and will be available in April 2020. The recommended dose is 100 mg every 3 months; some patients may benefit from a dose of 300 mg. Vyepti is the first FDA-approved intravenous (IV) treatment for migraine prevention.
Dr. Deborah Dunsire, President and CEO of Lundbeck, commented “With the approval of Vyepti, I am pleased that we are now able to offer a new IV therapy that achieves the key treatment goal of preventing migraine over time while also delivering on the need for earlier onset of efficacy. The Vyepti clinical program is the first to demonstrate this early benefit.”
The efficacy and safety of Vyepti was demonstrated in two phase III clinical trials (PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine).i The clinical trial program demonstrated a treatment benefit over placebo that was observed for both doses of Vyepti as early as day 1 post-infusion, and the percentage of patients experiencing a migraine was lower for VYEPTI than with placebo for most of the first 7 days. The safety of VYEPTI was evaluated in 2,076 patients with migraine who received at least one dose of Vyepti. The most common adverse reactions (≥2 percent and at least 2 percent or greater than placebo) in the clinical trials for the preventive treatment of migraine were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9 percent of patients treated with Vyepti discontinued treatment due to adverse reactions.
“The PROMISE-2 data showed that many patients can achieve reduction in migraine days of at least 75 percent and experience a sustained migraine improvement through 6 months, which is clinically meaningful to both physicians and patients,” said Dr. Peter Goadsby, a professor of neurology at King’s College, London and the University of California, San Francisco. “Vyepti is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease.”
About the PROMISE Clinical Trial Program
The efficacy of Vyepti™ (eptinezumab-jjmr) was evaluated as a preventive treatment of episodic and chronic migraine in two randomized, placebo-controlled studies, both with 6-month double-blind periods: one study in episodic (PROMISE-1; defined as 4-14 headache days per month, of which at least 4 were migraine days) and one study in patients with chronic migraine (PROMISE-2; defined as 15-26 headache days per month, of which at least 8 were migraine days).i In both studies, patients were randomized to receive placebo, Vyepti 100 mg, or Vyepti 300 mg. The primary endpoint was the change from baseline in mean MMD over months 1-3.i Patients were allowed to use concurrent acute migraine or headache medications, including migraine-specific medications (i.e., triptans, ergotamine derivatives), during the trial. Both studies excluded patients with a history of cardiovascular disease (hypertension, ischemic heart disease), neurological disease, and cerebrovascular disease. In PROMISE-2, the study population included patients with a dual diagnosis of chronic migraine and medication overuse headache attributable to acute-medication overuse of triptans, ergotamine, or combination analgesics greater than 10 days per month.
PROMISE-1: A total of 665 patients were randomized to receive placebo (N=222), 100 mg Vyepti (N=221), or 300 mg Vyepti (N=222) every 3 months for 12 months.
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 Vyepti 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.
Percent responders with at least 50 percent reduction in MMD in months 1-3 compared with placebo: 49.8 percent for 100 mg (nominal statistical significance p=0.009), 56.3 percent for 300 mg (p<0.001), and 37.4 percent for placebo
Percent responders with at least 75 percent reduction in MMD in months 1-3: 22.2 percent for 100 mg (p=NS*), 29.7 percent for 300 mg (p<0.001), and 16.2 percent for placebo.
Greater percentage of placebo-treated patients had migraine on most days during the first 7 days of treatment compared to Vyepti -treated patients.
*NS = Not statistically significant
PROMISE-2: A total of 1,072 patients were randomized to receive placebo (N=366), 100 mg Vyepti (N=356) or 300 mg Vyepti (N=350) every 3 months for 6 months
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 1-3: -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 percent reduction in MMD in months 1-3 compared with placebo: 57.6 percent for 100 mg (p<0.001), 61.4 percent for 300 mg (p<0.001), and 39.3 percent for placebo.
Percent responders with at least 75 percent reduction in MMD in months 1-3: 26.7 percent for 100 mg (p<0.001), 33.1 percent for 300 mg (p<0.001), and 15.0 percent for placebo.
Greater percentage of placebo-treated patients had migraine on each individual day during the first 7 days of treatment compared to Vyepti-treated patients.