Intranasal zavegepant offers rapid pain relief in patients with migraine

Treatment with zavegepant nasal spray provides pain and symptom relief in patients with migraine, according to a recent US study presented at AAN 2023.

Zavegepant was a recently FDA-approved intranasal formulation for the acute treatment of migraine, said Dr Richard Lipton from Albert Einstein College of Medicine in Bronx, New York, US, who presented the study.

“Non-oral acute treatments are recommended when oral forms are associated with an inadequate response, a slow response, or poor tolerability,” he noted. “Also, most people with migraine, when given a choice between nasal sprays and injectables, prefer nasal sprays.”

After nasal spray administration, significantly more patients treated with zavegepant attained freedom from pain within 2 hours than those treated with placebo (23.6 percent vs 14.9 percent; p<0.0001).

A significantly higher percentage of zavegepant-treated patients also achieved freedom from the most bothersome symptom (MBS) at 2 hours than the placebo-treated patients (39.6 percent vs 31.1 percent; p=0.012).

Taken together, the coprimary endpoints of this study in achieving freedom from pain and absence of MBS at 2 hours were met, said Lipton.

“This study provides evidence to support the use of non-oral delivery of a gepant in the acute treatment of migraine,” the researchers said in a recently published paper. [Lancet Neurol 2023;22:209-217]

This phase III, double-blind, placebo-controlled trial included 1,269 patients (mean age 40.8 years, 82.9 percent female) with migraine who had a history of 2–9 attacks per month. Participants were randomized to receive either zavegepant 10 mg nasal spray (n=623) or placebo (n=646) as treatment for a single migraine attack of moderate or severe pain intensity. [AAN 2023, abstract PL5.002]

As early as 15 minutes after the treatment dose, significantly more patients on zavegepant experienced rapid onset of pain relief than did those on placebo (15.9 percent vs 8.0 percent; p<0.0001).

The benefit seen with zavegepant vs placebo was sustained across all time points, at 30 minutes (30.5 percent vs 20.3 percent; p<0.0001), 60 minutes (43.3 percent vs 37.3 percent; p=0.0293), and 120 minutes after dosing (58.7 percent vs 49.7 percent; p=0.0012).

Due to the immediate pain relief, Lipton emphasized that most zavegepant recipients were able to return to their normal function as early as 30 minutes after treatment.

“Since part of the purpose of giving non-oral therapies to patients with migraine is a hope for rapid onset of action, the time-effect curve is relevant, and there were statistically significant effects of the zavegepant vs placebo,” said Lipton.

With regard to adverse events (AEs), dysgeusia, nasal discomfort, and nausea were the most commonly reported AEs, which were mostly considered mild or moderate. These AEs were anticipated given the nasal spray formulation and were similarly consistent with earlier research of zavegepant, Lipton said.

No serious AEs were reported in either treatment group. Zavegepant was well tolerated with a favourable safety profile, noted Lipton.

“Overall, zavegepant 10 mg nasal spray demonstrated a rapid onset of efficacy and sustained benefit, … as well as rapid restoration of normal function,” said Lipton. “Given that there are a billion people worldwide with migraine, … we now have a non-oral option for patients with migraine.”

“Many patients with migraine want a rapid onset of acute treatment effect, and not surprisingly, the onset of treatment effect is very much influenced by route of administration,” Lipton noted.