Eptinezumab eases migraine, medication-overuse headache

Two separate randomized controlled trials (SUNRISE and RESOLUTION) have shown the superiority of eptinezumab over placebo in a predominantly Asian migraine population and in patients with chronic migraine (CM) and medication-overuse headache (MOH).

In both studies, the effects were observed as early as day 1 and sustained through week 12, with a well-tolerated safety profile.

“Eptinezumab 100 and 300 mg demonstrated statistically significant greater reduction in monthly migraine days (MMDs) vs placebo, with better patient-reported outcomes,” according to the lead author of the SUNRISE study Dr Shengyuan Yu, Chinese PLA General Hospital, Beijing, China.

SUNRISE

A total of 978 participants (mean age 42 years, 86 percent female) were randomized in the SUNRISE trial (327 to eptinezumab 100 mg, 326 to eptinezumab 300 mg, and 325 to placebo), of whom 939 (95.5 percent) completed the placebo-controlled period. The majority of the participants were Asians (63.5 percent), with 17.4 mean MMDs at baseline. [EAN 2025, abstract EPR-040]

Both eptinezumab doses met the primary endpoint of mean change from baseline in MMDs over weeks 1‒12, which was significantly greater than that with placebo (100 mg: 7.2; p<0.0001; 300 mg: 7.5; p<0.0001; placebo: 4.8).

Furthermore, more participants treated with eptinezumab 100 and 300 mg vs placebo achieved reductions of ≥50 percent (37.8 percent and 42.9 percent vs 21.8 percent) and ≥75 percent (19.2 percent and 20.4 percent vs 7.7 percent) in MMDs through weeks 1‒12 from baseline. Both doses showed an odds ratio of >2 (p<0.0001) for ≥50-percent and ≥75-percent MMD responder rates.

“Improvements across patient-reported outcomes showed better effect with eptinezumab than placebo,” Yu said.

Treatment-emergent adverse events (TEAEs) occurred with similar frequency across groups: 100 mg (37.6 percent), 300 mg (32.2 percent), and placebo (33.5 percent). Serious TEAEs (<2 percent) or TEAEs leading to withdrawal (<2 percent) were rare. COVID-19 was the most common TEAE reported (100 mg: 5.5 percent; 300 mg: 4.6 percent; placebo: 4.3 percent).

RESOLUTION

In the RESOLUTION trial, 608 participants (mean age 45.5 years, 86 percent female, 98 percent from Europe) were randomized to eptinezumab 100 mg (n=305) or placebo (n=303). All participants received Brief Educational Intervention (BEI) about MOH prior to infusion. Of these, 596 (98.0 percent) completed the placebo-controlled period. [EAN 2025, abstract EPR-041]

At baseline, the participants had a mean of 20.9 MMDs, 21.7 monthly headache days (MHDs), and 20.1 monthly acute medication days (MAMDs) with acute medication use.

Participants treated with eptinezumab met the primary and key secondary endpoints, with a mean change from baseline in MMDs of ‒6.9 vs ‒3.7 with placebo (p<0.0001) through weeks 1‒4 and of ‒7.4 vs ‒4.5 through weeks 1‒12.

Eptinezumab also showed greater reductions in MHDs, MAMDs, and average daily pain (weeks 1‒2: ‒0.6 vs ‒0.3). Moreover, there were more participants in the eptinezumab vs the placebo arm who no longer fulfilled the criteria for CM (weeks 1‒4: 55.0 percent vs 32.4 percent; weeks 1‒12: 44.4 percent vs 23.0 percent) and MOH (weeks 1‒4: 52.2 percent vs 31.9 percent; weeks 1‒12: 40.1 percent vs 24.0 percent).

In terms of safety, the rate of TEAEs was comparable between arms (41.9 percent vs 36.9 percent).

“Eptinezumab was superior to placebo in reducing MMDs, MHDs, and acute medication use in patients with CM and MOH also receiving BEI,” said lead author Dr Rigmor H Jensen, Danish Headache Center, Department of Neurology, Rigshospitalet-Glostrup, University of Copenhagen, Copenhagen, Denmark

“These effects were evident across weeks 1‒4, sustained across weeks 1‒12, and extended to all key secondary endpoints,” he added.