FDA approval of Zavzpret provides another critical tool to combat migraine

The FDA approval of Zavzpret, which Pfizer announced in March 2023, is good news for people living with migraine, as it becomes an important option to help combat this disease.

According to a Pfizer press release, Zavzpret (zavegepant) is the first calcitonin gene-related peptide receptor (CGRP) antagonist nasal spray for acute migraine treatment in adults. Its approval was based on two pivotal studies that demonstrated efficacy, tolerability and safety of zavegepant over placebo.

In a phase 2/3, randomized, double-blind, placebo-controlled, dose-ranging study, single doses of zavegepant 10 mg and 20 mg were more effective than placebo for the acute treatment of migraine in adults and demonstrated a favorable safety profile (Croop et al).

In addition, a double-blind, randomized, placebo-controlled, phase 3 trial conducted at 90 academic medical centers, headache clinics and independent research facilities in the U.S. demonstrated that adults with a history of two to eight moderate or severe migraine attacks per month were free from pain and the most bothersome symptoms of migraine 2 hours after treatment with zavegepant 10 mg spray (Lipton et al). The most common adverse events in either treatment group were dysgeusia, nasal discomfort and nausea, with no evidence of hepatotoxicity reported.

Larry Charleston IV

Migraine is the second most disabling neurological disease globally (Feigin et al). According to Burch and colleagues in the journal, Headache, about one in six Americans report migraine or severe headache within a 3-month period.

The fast-acting nasal formulation of zavegepant — with positive results seen in about 15 minutes — has importance, as a goal of acute/abortive medications is to help restore people to function as soon as possible. Very few treatments work this fast.

All patients with migraine need acute treatment. While triptans are migraine-specific and should be offered to appropriate patients with migraine disease, not all patients respond, tolerate or are without comorbidities that may limit or prohibit the use of triptans. Another positive clinical aspect of CGRP-antagonist acute/abortive treatment is that, unlike triptans, they are not contraindicated in people with cardiovascular disease. Future studies demonstrating long-term efficacy and safety are needed.

Moreover, as shown in these studies, not all patients respond to zavegepant, and we still need other treatments for migraine disease. At the same time, it is great to have another option specifically designed for the acute/abortive treatment of migraine.

References:

• Burch R, et al. Headache. 2018;doi:org/10.1111/head.13281.
• Croop R, et al. Headache. 2022;doi:10.1111/head.14389.
• Feigin VL, et al. Lancet Neurol. 2019;doi:10.1016/S1474-4422(18)30499-X.
• Lipton RB, et al. Lancet Neurol. 2023;doi:10.1016/S1474-4422(22)00517-8.
• Pfizer’s Zavzpret (zavegepant) migraine nasal spray receives FDA approval. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-zavzprettm-zavegepant-migraine-nasal-spray. Published March 10, 2023.

For more information:

Larry Charleston IV, MD, MSc, FAHS, is professor and director of headache medicine and facial pain and faculty development in the department of neurology and ophthalmology at Michigan State University.