Zavegepant Nasal Spray Proves to Be an Effective Acute Migraine Treatment

Richard B. Lipton, MD

Recent findings from a phase 3, double-blind, randomized, placebo-controlled trial (NCT04571060) showed zavegepant (Zavzpret; Pfizer), a calcitonin gene-related peptide (CGRP) receptor antagonist, as an effective acute treatment for migraine as it achieved its coprimary end points.¹

Compared with the placebo group, zavegepant proved superior for pain freedom (23.6% vs 14.9%; P <.0001) and freedom from the most bothersome symptom (MBS; 39.6% vs 31.1%; P = .0012) at 2 hours post dose. Senior author Richard B. Lipton, MD, director, Montefiore Headache Center, and colleagues presented the resultsat the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts.

The trial included adult patients with a history of between 2 and 8 moderate or severe monthly migraine attacks, who then self-administered 1 dose of zavegepant 10-mg nasal spray or placebo to treat 1 migraine attack of moderate or severe pain intensity. Freedom from pain and freedom from the MBS at 2 hours post dose were the coprimary efficacy end points. Among the 1405 randomized participants, 1269 (mean age 41 years) were evaluable for efficacy (zavegepant, n = 623; placebo, n = 646).

On the secondary end point of pain relief, zavegepant showed significant improvement at 15 minutes (15.9% vs 8.0%; P <.0001) and 2 hours (58.7% vs 49.7%; P = .0012). Additional secondary end points were also significant, which included the return to normal function at 30 minutes (10.5% vs 6.1%; P = .0059) and 2 hours (35.8% vs 25.6%; P = .0001), and sustained pain relief 2 to 48 hours post dose (36.1% vs 29.6%; P = 0.013).

Most adverse events zavegepant vs placebo in patients were mild or moderate and none were serious. The most common ones were dysgeusia (20.5% vs 4.7%), nasal discomfort (3.7% vs .8%), and nausea (3.2% vs 1.1%).

Zavegepant is the only small molecule CGRP receptor antagonist delivered by nasal spray available for the acute treatment of migraine. In March 2023, the treatment was approved by the FDA for the acute treatment of migraine with or without aura in adults.² The approval was supported by 2 pivotal double-blind, placebo-controlled studies (NCT03872453; NCT04571060).

One of the trials (NCT03872453) assessed the agent in forms of 5-, 10-, and 20-mg doses vs placebo in a cohort of 1673 patients with migraine. All told, zavegepant 10 mg and 20 mg were more effective than placebo on the coprimary end points of pain freedom at 2 hours postdose (placebo: 15.5% [98.3% CI, 11.1, 19.8]; 10 mg: 22.5% [98.3% CI, 17.5, 27.6; P = 0.0113]; 20 mg: 23.1% [98.3% CI, 18.1, 28.2; P = 0.0055]) and freedom from the MBS at 2 hours post dose (placebo: 33.7% [98.3% CI, 28.0, 39.3]; 10 mg: 41.9% [98.3% CI, 36.0, 47.9; P = 0.0155]; 20 mg: 42.5% [98.3% CI, 36.6, 48.4; P = 0.0094]).³

The agent also demonstrated a duration and sustained effect profile through 48 hours (nominal P <.05) in the previous trial. This included sustained pain freedom 2 to 24 hours (5 mg, 10 mg, and 20 mg), sustained pain freedom 2 to 48 hours (5 mg, 10 mg, and 20 mg), sustained pain relief 2 to 24 hours (5 mg, 10 mg, and 20 mg), and sustained pain relief 2 to 48 hours (5 and 10 mg).

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REFERENCES
1. Mullin K, Croop R, Pavlovic J, et al. Efficacy and Safety of Zavegepant Nasal Spray for the Acute Treatment of Migraine: Results of a Phase 3 Double-Blind, Randomized, Placebo Controlled Trial. Presented at: 2023 AAN Annual Meeting; April 22-27, Boston, Massachusetts.
2. Pfizer’s Zavzpret (zavegepant) migraine nasal spray receives FDA approval. News release. Pfizer. March 10, 2023. Accessed April 22, 2023. https://www.businesswire.com/news/home/20230309005795/en/Pfizer%E2%80%99s-ZAVZPRET%E2%84%A2-zavegepant-Migraine-Nasal-Spray-Receives-FDA-Approval
3. Biohaven achieves positive topline results in pivotal phase 2/3 study of vazegepant, the first and only intranasal CGRP receptor antagonist in clinical development for the acute treatment of migraine. News release. December 17, 2019. Accessed April 22, 2023. https://www.prnewswire.com/news-releases/biohaven-achieves-positive-topline-results-in-pivotal-phase-23-study-of-vazegepant-the-first-and-only-intranasal-cgrp-receptor-antagonist-in-clinical-development-for-the-acute-treatment-of-migraine-300976000.html