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The PROMISE-2 clinical trial data suggest that the recently approved, IV-administered eptinezumab (Vyepti; Lundbeck) is effective in both 100- and 300-mg doses for patients with chronic migraine.
Richard Lipton, MD
Data from the PROMISE-2 clinical trial (NCT02974153) of eptinezumab (Vyepti; Lundbeck) in the prevention of migraine suggest that both the 100- and 300-mg doses are associated with significant reductions in monthly migraine days, beginning the day after intravenous (IV) administration, providing Class I evidence for a single dose.1
Notably, the percentages of patients with a migraine on day 1 post-infusion were 28.6% and 27.8% for the 100- and 300-mg doses, respectively, compared to 42.3% for placebo. At baseline, the average level was 58% for the cohort during the 28-day lead-in period.
This full data set was published in Neurology. The therapy was approved by the FDA in late February 2020, based on the findings of these data, as well as those of the PROMISE-1 clinical trial (NCT02559895). Lundbeck noted that the recommended dose of its anti-calcitonin gene-related peptide (CGRP) prophylactic is 100 mg, to be administered quarterly, though some may benefit from a 300-mg dose.2
“The PROMISE 2 study found that VYEPTI is associated with a clinically meaningful migraine preventive effect over multiple efficacy measures and is well tolerated in adults with chronic migraine,” lead author Richard B. Lipton, MD, director, Montefiore Headache Center, and professor of neurology, Albert Einstein College of Medicine, said in a statement. “The early onset of effect we saw with VYEPTI in this study may translate into meaningful benefits for patients with chronic migraine and may allow them to get back to work, school, household, and family obligations sooner.”
Overall, PROMISE-2 included 1072 participants with chronic migraine and a mean number of baseline monthly migraine days of 16.1. A total of 1049 patients (93.6%) completed through Week 12, while 1000 patients (89.2%) attended the week 24 visit and 878 patients (78.3%) attended the week 32 visit.
After 12 weeks, those treated with 100- and 300-mg doses of eptinezumab experienced significant reductions of 7.7 (P <.0001) and 8.2 (P <.0001) days, respectively, compared to a 5.6-day reduction for the placebo group.
The secondary end point of ≥75% response was achieved by a larger percentage of those in the treatment groups compared to placebo, with the 100-mg group having an odds ratio [OR] of 2.4 (95% CI, 1.7—3.5) and the 300-mg group having an OR of 3.2 (95% CI, 2.2–4.6) for the first 4 weeks of treatment. Over the full 12-week study period, the results were similar for both the 100-mg (OR, 2.0; 95% CI, 1.4–3.0) and 300-mg (OR, 2.8; 95% CI, 1.9–4.0) groups.
Additionally, the odds of ≥50% response during Weeks 1 to 12 were higher for both the 100-mg (OR, 2.1; 95% CI, 1.6—2.8) and 300-mg (OR, 2.4; 95% CI, 1.8–3.3) groups compared to placebo.
“The publications of PROMISE 2 and PROMISE 1 in Neurology and Cephalalgia, respectively, underscore the scientific support of Vytepi as a powerful and generally well-tolerated preventive therapy with 4 infusions a year,” said Roger Cady, MD, head, Neurology Medical, Lundbeck Seattle Biopharmaceuticals, in a statement. “These publications also further highlight the design of VYEPTI as an IV infusion to deliver 100 percent of the medicine into the bloodstream by the end of the infusion.”
Despite not being included in the prespecified testing algorithm for the 100-mg group, Headache Impact Test (HIT-6) scores were also reduced significantly for both groups from baseline. For the 100-mg group, of which 89.6% were severe (mean score, 65) at baseline, the percent of severe-range scores was lowered to 51.4% (mean score difference from placebo, —1.7 (P = .001). For the 300-mg group, 88.6% were in the severe-score range (mean score, 65.1) at baseline, which was reduced to 42.9% (mean score difference from placebo, —2.9; 95% CI, –3.9 to –1.8; P <.0001). Comparatively 87.4% of the placebo group (mean score, 64.8) had severe-range scores at baseline, which was reduced to 60.1% after 12 weeks.
As for safety, treatment-emergent adverse events (AEs) were reported by 43.5% (100 mg), 52.0% (300 mg), and 46.7% (placebo) of patients. Nasopharyngitis was the only AE reported for >2% of eptinezumab-treated patients—which was also >2% more than placebo—occurring in the 300-mg eptinezumab arm (eptinezumab, 9.4%; placebo, 6.0%).
1. Lipton RB, Goadsby PJ, Smith J, et al. Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology. 2020;94(13). Published online March 25, 2020. doi: 10.1212/WNL.0000000000009169.
2. VYEPTI™ (eptinezumab-jjmr) Demonstrated Significant Positive Impact in Prevention of Chronic Migraine in Adults, Pivotal Phase III Study Published in Neurology Finds [press release]. Deerfield, IL: Lundbeck; Published March 25, 2020. Accessed March 31, 2020. businesswire.com/news/home/20200325005374/en/VYEPTI%E2%84%A2-eptinezumab-jjmr-Demonstrated-Significant-Positive-Impact-Prevention