Phase 3 Data Published for Zavegepant for the Acute Treatment of Migraine in Adults

A single 10-mg dose of zavegepant nasal spray is an effective acute treatment for migraine, according to data published in The Lancet Neurology.¹ The data came from a phase 3 clinical trial of zavegepant, which is an investigational calcitonin gene-related peptide receptor anatagonist nasal spray for the acute treatment of migraine in adults.

“The results from this study demonstrate zavegepant’s potential as an effective acute nasal spray treatment for migraine, a neurological disorder that affects more than one billion people worldwide,” Richard B. Lipton, MD, lead author, Department of Neurology at the Albert Einstein College of Medicine, said in a statement.²

The study met its co–primary end points of showing a single 10-mg dose of zavegepant was more effective than the placebo for pain freedom and freedom from the most bothersome symptom at 2 hours post-dose. Zavegepant also demonstrated relief from migraine pain in 15 minutes and relief lasted for up to 48 hours for many patients.

The trial consisted of 1405 people who were randomized to receive a single 10-mg dose of either zavegepant or the placebo. The participants had a history of experiencing 2 to 8 moderate or severe migraine attacks per month, lasting a mean of 30.8 hours untreated. Participants were asked to record their migraine headache pain intensity on a 4-point scale, their most bothersome migraine symptom, and their level of functional disability immediately before dosing the treated attack and during intervals post-dose.

Zavegepantwas superior to the placebo on the co–primary efficacy endpoints of pain freedom (24% vs 15% P<0·0001) and freedom from the most bothersome symptom (40% vs 31%, P= .0012) at 2 hours post-dose.

Furthermore, zavegepant was more effective than the placebo in 13 out of 17 secondary endpoints. Zavegepant was associated with higher rates of return to normal functional ability at 30 minutes and 2 hours post treatment. However, the difference between zavegepant and placebo was not significant for return to normal function at 15 minutes post-dose.

Although zavegepant was well tolerated, the most common adverse event (AE) in either treatment group (≥2%) was an altered sense of taste, which occurred in 20.5% of patients receiving the drug. Nasal discomfort occurred in 3.7% of patients receiving zavegepant and nausea occurred in 3.2%. The AE safety profile was consistent with earlier studies of the drug.

No serious AEs were reported in the treated patients.

Zavegepant is a third-generation, high affinity, selective and structurally unique, small molecule CGRP receptor antagonist. It is the only CGRP receptor antagonist in clinical development with both oral and intranasal formulations.

“The intranasal formulation for zavegepant embodies breakthrough innovation in patient-centric drug development,” said James Rusnak, MD, PhD, senior vice president, chief development officer, Internal Medicine and Hospital, Global Product Development at Pfizer. “If approved by the FDA, zavegepant has the potential to be a significant new treatment option for people with migraine, particularly those who desire fast-acting relief or would benefit from an alternative delivery method.”

There is a New Drug Application filed with the FDA for intranasal zavegepant for acute treatment of migraine in adults. The FDA is expected to make a decision by the end of the first quarter.

References

1. Lipton R, et al. Safety, tolerability, and efficacy of zavegepant 10 mg nasal spray for the acute treatment of migraine in the USA: a phase 3 double-blind, randomised, placebo-controlled multicentre trial. The Lancet Neurology. 2023; 22(3) DOI: https://doi.org/10.1016/S1474-4422(22)00517-8

2. Pfizer announces The Lancet Neurologyhas published phase 3 data for zavegepant for the acute treatment of migraine in adults. News release. February 16, 2023. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-lancet-neurology-has-published-phase-3