Fast-Acting Nasal Spray for Migraine Snags FDA Approval

The FDA approved intranasal zavegepant (Zavzpret) for acute migraine, making it the first calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray with this indication, drugmaker Pfizer announced on Friday.

Zavegepant is indicated for the treatment of migraine with or without aura, and is not indicated for preventing migraine.

The pathophysiology of migraines is related to CGRP pathways, and CGRP inhibitor drugs, both oral and injectable, have been approved in the last few years for acute treatment and the prevention of migraine.

“Among my migraine patients, one of the most important attributes of an acute treatment option is how quickly it works. As a nasal spray with rapid drug absorption, [zavegepant] offers an alternative treatment option for people who need pain relief or cannot take oral medications due to nausea or vomiting, so they can get back to normal function quickly,” said Kathleen Mullin, MD, of the New England Institute for Neurology & Headache in Stamford, Connecticut, in the statement from Pfizer.

Zavegepant’s approval was based on two phase III trials that demonstrated its safety and efficacy for the acute treatment of migraine.

In one of the pivotal trials, findings of which were presented at the 2022 American Headache Association meeting and recently published in Lancet Neurology, intranasal administration with the CGRP receptor antagonist was found to be significantly superior to placebo on the co-primary endpoints of pain freedom (23.6% vs 14.9%, P<0.0001) and freedom from the most bothersome symptom (39.6% vs 31.1%, P=0.0012) at 2 hours post-dose.

The trial also demonstrated superiority to placebo across 13 of 17 prespecified secondary outcome measures. At 15 minutes post-dose, 15.9% of the zavegepant group reported pain relief, compared with 8.0% of the placebo group. And at 30 minutes post-dose, those numbers increased to 30.5% and 20.3% for the two groups, respectively (P<.0001 for all).

In clinical trials for zavegepant, the most common adverse reactions occurring at a frequency greater than with placebo were taste disorders (including dysgeusia and ageusia), nausea, nasal discomfort, and vomiting.

Zavegepant is contraindicated in patients with a history of hypersensitivity to it or any of its components. Hypersensitivity reactions, including facial swelling and urticaria, have occurred in clinical trials, Pfizer noted.

The company said it plans to start making the nasal spray available in pharmacies in July 2023.