番茄社区

LOS ANGELES -- Eptinezumab, an intravenous calcitonin gene-related peptide (CGRP) inhibitor, met its primary endpoint in the phase III PROMISE 2 trial of chronic migraine prevention, reported researchers here at the American Academy of Neurology annual meeting.

Eptinezumab decreased monthly migraine days in chronic migraine patients by about 50%, from a baseline of about 16 days a month, over 12 weeks, reported Richard Lipton, MD, of the Montefiore Headache Center in New York City. These patients had significantly fewer monthly migraine days with 100 mg (-7.7 days) and 300 mg (-8.2 days) infusions of eptinezumab, compared with placebo (-5.6 days).

One-third of people who had the highest dose of eptinezumab had a 75% or greater reduction in their headache frequency, Lipton added.

also demonstrated eptinezumab's rapid effect: the percentage of patients who had a migraine one day after infusion dropped by approximately 50%.

This result shouldn't be surprising, said David Dodick, MD, of the Mayo Clinic in Phoenix, who was not involved in this research but was a co-author on last year's PROMISE 1 study.

"Oral small-molecule CGRP antagonists like ubrogepant are effective for the acute treatment of migraine, so if we infused a patient with an antibody that has 100% bioavailability, it's going to have an acute treatment effect," Dodick told 番茄社区. "It appears that, 24 hours after an eptinezumab infusion, there's a significant reduction in the percentage of patients who have a migraine on that particular day, and that effect appears to be sustained."

Of the four anti-CGRP monoclonal antibodies being developed to prevent migraine, eptinezumab is the only one that's intravenous. Erenumab (Aimovig), galcanezumab, and fremanezumab are delivered by subcutaneous injections.

In the clinical trial plenary session where Lipton presented the PROMISE 2 results, Natalia Rost, MD, of Massachusetts General Hospital in Boston and chair of the AAN meeting scientific committee, echoed concerns from physicians about the long-term effects of blocking CGRP.

"Obviously, with new molecular entities, you don't know what you don't know," Lipton replied. "All four companies developing CGRP monoclonal antibodies and both companies developing gepants -- small-molecule receptor antagonists -- are conducting long-term safety studies. And my sense of the data I've seen so far is that the safety and the tolerability profiles of CGRP-targeted therapies look really excellent."

CGRP is the most potent vasodilator in the body and after hypertension, migraine with aura is the second most powerful risk factor from an attributable risk perspective for stroke, he added. "The idea of blocking the vasodilatory system in a group of patients that has a risk factor for stroke has been a source of some concern. Thus far, there's no evidence of complications related to vascular disease.

"The data that's available is really reassuring, but, of course, these drugs have been administered to thousands of people, and not the hundreds of thousands or millions of people who may ultimately receive them, so we do have to wait for the long-term safety data," he added.

Last year, PROMISE 1 demonstrated that, in patients with frequent, episodic migraines, eptinezumab didn't fare much better than placebo. Over 12 weeks, these patients had fewer monthly migraine days with 30 mg (-4.0 days), 100 mg (-3.9 days), and 300 mg (-4.3 days) infusions of eptinezumab, compared with placebo (-3.2 days).

This year, an exploratory analysis of PROMISE 1 showed that were associated with incremental reductions in migraine frequency at 6 months. Another PROMISE 1 analysis showed that episodic migraine patients who received 300 mg of eptinezumab and who achieved a 75% or greater reduction in migraine days from baseline experienced longer migraine-free intervals that corresponded with meaningful improvements in a .

Observed eptinezumab side effects continue to be upper respiratory infections, common colds, and sinusitis.

"These preliminary results suggest that a select group of patients may have significant benefit in migraine prevention," Mia Minen, MD, of NYU Langone Health in New York City, who did not participate in either eptinezumab trial, told 番茄社区.

Many patients struggle with adhering to the currently available migraine treatments, she added: "If larger and more long-term studies indicate that the safety profile continues to be okay, these medications may be a useful option for preventing migraines."