Abstract
Introduction
Zavegepant is a small-molecule calcitonin gene-related peptide receptor blocker (gepant). Gepants may be particularly useful in people who are triptan insufficient responders (TIR) and/or have contraindications for use of triptans.
Methods
Post hoc analyses of efficacy and safety from the development program for zavegepant 10 mg nasal spray for the treatment of acute migraine in adults by baseline triptan experience. Pooled efficacy data from two double-blind, single-dose, randomized, placebo-controlled trials (NCT03872453, NCT04571060) were used to assess efficacy; co-primary efficacy endpoints were pain freedom (2 h PF) and most bothersome symptom (2 h MBS) freedom at 2 hours post-dose. Safety assessments included adverse events (AEs) from the 1-year, multiple-dose, open-label study (NCT04408794). Participants were grouped based on triptan use into a triptan naïve group (never used a triptan), TIR (used ≥1 triptans but not currently on a triptan), and current triptan users.
Results
Overall, 2061 (pooled efficacy analysis set) and 603 (long-term safety analysis set) participants were included. In pooled analyses, 2 h PF rates for zavegepant versus placebo were 21.0% versus 11.9% (p=0.0254) for current triptan users, 24.8% versus 17.4% (p=0.0029) for triptan-naïve, and 21.8% versus 12.6% (p=0.0024) for TIR. For 2 h MBS freedom, corresponding rates were 40.0% versus 29.5% (p=0.0440), 40.4% versus 34.0% (p=0.0303), and 41.0% versus 29.9% (p=0.0035). In long-term safety analyses, incidences of AEs, serious AEs, and AEs leading to discontinuation were generally consistent across subgroups, regardless of triptan experience.
Conclusion
In these post hoc analyses, response rates favored zavegepant versus placebo for the acute treatment of migraine, regardless of triptan experience. Zavegepant was well tolerated.
Keywords: efficacy, migraine, risk factors, safety, triptans, zavegepant
Introduction
Migraine is a significant cause of disability1–4 and is associated with a substantial burden for both individuals5–7 and society.8–13 Variability in migraine characteristics between people necessitates an individualized treatment plan that may include a preventive treatment to reduce attack frequency and severity, and an acute treatment to rapidly treat migraine attacks.14,15 Triptans are among the specific acute treatment options for migraine.14,15 In many cases triptans are effective and well tolerated,16,17 but they are not suitable for everyone; some people experience insufficient efficacy from or lack of tolerability to triptans.18,19 Two recent systematic reviews concluded that there is a large population of people living with migraine whose needs are not met by triptans.18,20
Zavegepant is a small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist, a gepant administered by nasal spray, indicated for the acute treatment of migraine with or without aura in adults. The efficacy of single doses of zavegepant for the acute treatment of migraine was demonstrated in two double-blind, placebo-controlled clinical trials, both of which met their co-primary endpoints.21,22 The safety of multiple doses of zavegepant, when used up to 8 times a month for up to 52 weeks for the acute treatment of migraine, was demonstrated in an open-label safety study.23
In these post hoc analyses, we investigate the efficacy and safety of zavegepant in people with migraine based on their prior experience with triptans. The aim of the current analyses was to explore the efficacy and safety of zavegepant according to baseline triptan experience.
Methods
Study Design
These post hoc subgroup analyses were based on the data from three studies of zavegepant for the acute treatment of migraine: two double-blind, single-dose, randomized, placebo-controlled trials (Studies 201 and 301: NCT03872453,21 NCT04571060,22 respectively) and a 1-year, multiple-dose open-label safety study (NCT0440879423). Eligible participants for these studies were adults ≥18 years of age with ≥1-year history of migraine (with or without aura),24 and a history of 2–8 migraine attacks per month of moderate or severe pain intensity.
Efficacy data were pooled from a single-dose Phase 2/3 trial (Study 201, NCT0387245321) and a Phase 3 trial (Study 301, NCT0457106022). Both studies were double-blind, randomized, placebo-controlled trials. Full methodologies for these studies have been published previously.21,22 Participants eligible for the pooled analysis treated a single migraine attack of moderate or severe pain intensity with zavegepant 10 mg nasal spray or placebo. Co-primary endpoints were the percentage of participants with pain freedom and most bothersome symptom (MBS) freedom at 2 hours post-dose. Pain freedom was defined as the transition from moderate to severe pain intensity at baseline to a pain intensity of 0 at 2 hours post-dose. Pain intensity was measured on a 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). Prior to treatment, participants identified their MBS (selected from nausea, phonophobia, or photophobia). MBS freedom at 2 hours was defined by the absence of the participant designated MBS at 2 hours post-dose, with symptom status measured on a binary scale (0=absent, 1=present). Secondary and exploratory endpoints included the percentage of participants with pain relief and return to normal function at all timepoints (15, 30, 45, 60, 90, and 120 minutes) post-dose. Pain relief was defined as a pain intensity of none or mild at a timepoint post-dose. Return to normal function was defined as a functional disability level of normal at a timepoint post-dose in the subset of participants with functional disability at the time of dosing. Functional disability level was measured on a 4-point numeric rating scale (0=normal, 1=mildly impaired, 2=severely impaired, 3=requires bedrest).
Safety data were from a Phase 2/3, multicenter, open-label, single-arm, long-term safety study of zavegepant for the acute treatment of migraine (Study 202, NCT0440879423). Participants treated migraine attacks of any intensity as needed with one dose of zavegepant 10 mg nasal spray, up to once per day and up to 8 times per month (28 days), for up to 52 weeks. The primary endpoints included the incidences (i.e., number and percentage of participants) of on-treatment adverse events (AEs), serious AEs, and AEs leading to discontinuation. AEs of special interest included medication overuse headache, hepatic-related AE, potential drug abuse, local irritation, cardiovascular AE, and suicidality.
Statistical Analyses
Post hoc subgroup analyses were conducted in the pooled efficacy analysis set and the long-term safety analysis set according to baseline triptan experience. Participants were grouped according to baseline triptan experience into 3 groups: current triptan user (current triptan use), triptan-naïve (no current triptan use and no historical use of discontinued triptans), and triptan insufficient responders (TIR; historical use of one or more discontinued triptans and not currently on a triptan). For the purposes of these post hoc analyses, the TIR group included participants who had prior triptan discontinuation for any reason, including insufficient response (lack of efficacy) and/or tolerability, and included any formulation (nasal, oral, subcutaneous, and/or other) of almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan, or the sumatriptan-naproxen combination. It was assumed that if a participant took a triptan and responded sufficiently that they would continue therapy. Definitions of triptan insufficient responders have been reviewed and this approach is well precedented in prior literature.20,25–27
The pooled efficacy analysis set (in the two single-dose Studies 201 and 301) was defined as randomized participants who were treated with study drug, had a migraine of moderate or severe pain intensity at the time of dosing, and had post-dose efficacy data. For all efficacy endpoints, participants with missing data at the time point of interest or who took rescue medication at or before the time point of interest were classified as failures. Treatment groups were compared using Mantel-Haenszel risk estimation with stratification by study. As this is a post hoc analysis, p-values are nominal.
The long-term safety analysis set (in the multiple-dose Study 202) was defined as enrolled participants who were treated with zavegepant. AEs were coded using MedDRA version 24.0. On-treatment AEs were defined as those with onset on or after the first dose of zavegepant through the last dose of zavegepant plus 7 days.
Results
Demographics
Overall, the pooled efficacy analysis set included 2061 participants, and all 2061 were evaluated according to prior triptan experience. The long-term safety analysis set included 603 participants, all of whom were included in all safety analyses.
The demographic and baseline characteristics of the pooled efficacy data set based on triptan experience are shown in Table 1. The zavegepant and placebo groups were generally similar within triptan experience categories. In the triptan-naïve group, participants were slightly younger, more likely to be male and Hispanic, and less likely to have received preventive medication.
Table 1.
Demographics and Baseline Characteristics of the Pooled Efficacy Analysis Set, According to Baseline Triptan Experience
| Current Triptan User | Triptan-Naïve | TIR | ||||
|---|---|---|---|---|---|---|
| Zavegepant 10 mg (n=195) |
Placebo (n=176) |
Zavegepant 10 mg (n=512) |
Placebo (n=570) |
Zavegepant 10 mg (n=307) |
Placebo (n=301) |
|
| Age at informed consent, years | ||||||
| Mean (SD) | 43.3 (13.4) | 43.5 (14.3) | 39.1 (12.7) | 38.3 (12.8) | 43.1 (13.2) | 42.7 (11.5) |
| Sex, n (%) | ||||||
| Female | 169 (86.7) | 154 (87.5) | 397 (77.5) | 457 (80.2) | 273 (88.9) | 273 (90.7) |
| Male | 26 (13.3) | 22 (12.5) | 115 (22.5) | 113 (19.8) | 34 (11.1) | 28 (9.3) |
| Race, n (%) | ||||||
| White | 175 (89.7) | 162 (92.0) | 368 (71.9) | 452 (79.3) | 264 (86.0) | 254 (84.4) |
| Black or African American | 15 (7.7) | 4 (2.3) | 113 (22.1) | 97 (17.0) | 29 (9.4) | 40 (13.3) |
| American Indian or Alaska Native | 0 | 2 (1.1) | 0 | 1 (0.2) | 0 | 0 |
| Asian | 3 (1.5) | 5 (2.8) | 23 (4.5) | 17 (3.0) | 7 (2.3) | 6 (2.0) |
| Native Hawaiian or Other Pacific Islander | 1 (0.5) | 0 | 0 | 1 (0.2) | 2 (0.7) | 0 |
| Multiple | 1 (0.5) | 3 (1.7) | 8 (1.6) | 2 (0.4) | 5 (1.6) | 1 (0.3) |
| Ethnicity, n (%) | ||||||
| Hispanic or Latino | 19 (9.7) | 24 (13.6) | 138 (27.0) | 170 (29.8) | 24 (7.8) | 32 (10.6) |
| Not Hispanic or Latino | 176 (90.3) | 152 (86.4) | 374 (73.0) | 400 (70.2) | 283 (92.2) | 269 (89.4) |
| BMI, kg/m2 | ||||||
| Mean (SD) | 27.33 (4.8) | 26.23 (4.8) | 27.58 (4.9) | 27.58 (4.8) | 27.15 (4.7) | 28.06 (4.8) |
| Preventive migraine medication use at randomization, n (%) | 40 (20.5) | 39 (22.2) | 27 (5.3) | 27 (4.7) | 71 (23.1) | 70 (23.3) |
Abbreviations: BMI, body mass index; SD, standard deviation; TIR, triptan insufficient responder.
The demographic and baseline characteristics of the long-term safety analysis data set by triptan experience are shown in Table 2. Participants in the triptan-naïve group were younger and more likely to be male, Black, or Hispanic.
Table 2.
Demographics and Baseline Characteristics of the Long-Term Safety Analysis Set, According to Baseline Triptan Experience
| Current Triptan User (n=121) |
Triptan-Naïve (n=242) |
TIR (n=240) |
|
|---|---|---|---|
| Age at informed consent, years | |||
| Mean (SD) | 45.1 (12.5) | 39.2 (11.9) | 43.4 (12.5) |
| Sex, n (%) | |||
| Female | 106 (87.6) | 191 (78.9) | 220 (91.7) |
| Male | 15 (12.4) | 51 (21.1) | 20 (8.3) |
| Race, n (%) | |||
| White | 110 (90.9) | 188 (77.7) | 204 (85.0) |
| Black or African American | 7 (5.8) | 37 (15.3) | 26 (10.8) |
| American Indian or Alaska Native | 0 | 0 | 2 (0.8) |
| Asian | 4 (3.3) | 13 (5.4) | 6 (2.5) |
| Native Hawaiian or Other Pacific Islander | 0 | 2 (0.8) | 0 |
| Multiple | 0 | 2 (0.8) | 2 (0.8) |
| Ethnicity, n (%) | |||
| Hispanic or Latino | 12 (9.9) | 40 (16.5) | 19 (7.9) |
| Not Hispanic or Latino | 109 (90.1) | 202 (83.5) | 221 (92.1) |
| BMI, kg/m2 | |||
| Mean (SD) | 26.4 (4.1) | 26.7 (3.9) | 26.0 (4.0) |
Abbreviations: BMI, body mass index; SD, standard deviation; TIR, triptan insufficient responder.
Migraine History
The mean (standard deviation [SD]) number of moderate to severe migraine attacks at baseline was 4.7 (1.8) for the zavegepant group and 4.8 (1.8) for the placebo group in the pooled study analysis set (n=2061) and 5.0 (1.9) for the long-term safety analysis set (n=603). Corresponding average duration of untreated migraine attacks was 30.7 (21.5) hours, 31.8 (21.8) hours, and 30.1 (20.9) hours. The primary migraine type was migraine without aura for 68.9% of participants in the zavegepant group and 67.0% in the placebo group in the pooled efficacy analysis set (n=2061), and 74.0% of participants in the long-term safety analysis set (n=603). Nausea, photophobia, and phonophobia, respectively, were the reported MBS by 26.0%, 58.6%, and 15.4% of participants in the zavegepant group and 23.3%, 61.8%, and 14.9% of participants in the placebo group in the pooled efficacy analysis set (n=2061), and 29.7%, 51.9%, and 18.4% of participants in the long-term safety analysis set (n=603).
Efficacy According to Triptan Experience in the Pooled Efficacy Analysis Set
For zavegepant versus placebo, response rates for pain freedom at 2 hours post-dose were 21.0% versus 11.9% (p=0.0254) in current triptan users, 24.8% versus 17.4% (p=0.0029) in the triptan-naïve subgroup, and 21.8% versus 12.6% (p=0.0024) in the TIR subgroup (Figure 1). Similarly, response rates for MBS freedom at 2 hours post-dose were 40.0% versus 29.5% (p=0.0440) in current triptan users, 40.4% versus 34.0% (p=0.0303) in the triptan-naïve subgroup, and 41.0% versus 29.9% (p=0.0035) in the TIR subgroup (Figure 1). For all three triptan-experience subgroups, across most timepoints, response rates for pain relief and return to normal function favored zavegepant 10 mg nasal spray compared with placebo (Figure 2).
Figure 1.
Percentages (95% CI) of participants with pain freedom at 2 hours post-dose (a) and MBS freedom at 2 hours post-dose (b) in the pooled efficacy analysis set by baseline triptan experience. Stratified by study using Mantel-Haenszel risk estimation. Participants with missing data at the time point of interest or who took rescue medication at or before the time point of interest were classified as failures. All p-values are nominal.
Abbreviations: CI, confidence interval; MBS, most bothersome symptom; TIR, triptan insufficient responder.
Figure 2.
Percentages (95% CI) with pain relief (a) and return to normal function (b) through 2 hours post-dose in the pooled efficacy analysis set, by baseline triptan experience. Stratified by study using Mantel-Haenszel risk estimation. Participants with missing data at the time point of interest or who took rescue medication at or before the time point of interest were classified as failures. Return to normal function assessed in participants with functional disability at the time of dosing.
Abbreviations: CI, confidence interval; TIR, triptan insufficient responder.
Exposure to Zavegepant in the Long-Term Safety Analysis Set
Exposure to zavegepant was generally comparable among participants regardless of triptan experience (Table 3).
Table 3.
Exposure to Zavegepant in the Long-Term Safety Analysis Set, According to Baseline Triptan Experience
| Current Triptan User (n=121) |
Triptan-Naïve (n=242) |
TIR (n=240) |
|
|---|---|---|---|
| Time on zavegepant, weeks | |||
| Mean (SD) | 34.2 (20.2) | 37.6 (18.0) | 34.1 (19.5) |
| Median (min, max) | 47.7 (0.1, 52.4) | 49.1 (0.1, 54.3) | 47.2 (0.1, 54.9) |
| Average exposure, sprays per montha | |||
| Mean (SD) | 3.0 (1.6) | 3.1 (1.6) | 3.1 (1.6) |
| Median (min, max) | 2.8 (0.5, 7.7) | 2.8 (0.4, 7.8) | 2.9 (0.3, 7.9) |
| Cumulative exposure to zavegepant, sprays | |||
| Mean (SD) | 30.3 (23.6) | 32.7 (22.3) | 30.3 (23.0) |
| Median (min, max) | 30.0 (1.0, 99.0) | 29.5 (1.0, 104.0) | 29.0 (1.0, 101.0) |
Notes: Sprays per month are based on 4-week intervals in the long-term treatment (LTT) phase. a Derived as (1) cumulative zavegepant exposure (sprays) if time in the LTT period <2 weeks, or (2) 4 × cumulative zavegepant exposure/time in the LTT period if time in the LTT period ≥2 weeks.
Abbreviations: Max, maximum; Min, minimum; SD, standard deviation; TIR, triptan insufficient responder.
Safety According to Triptan Experience in the Long-Term Safety Analysis Set
The incidence of on-treatment AEs was generally comparable regardless of triptan experience (Table 4). On-treatment AEs were reported by 76.9%, 74.0%, and 78.3% of participants in the current triptan user, triptan-naïve, and TIR subgroups, respectively. The most common AEs across these subgroups were dysgeusia and nasal discomfort. Most AEs were mild to moderate in intensity, with severe AEs reported by 6.6%, 1.7%, and 4.2% of participants in the current triptan user, triptan-naïve, and TIR subgroups, respectively. Correspondingly, serious AEs were reported by 0%, 1.2%, and 1.7% of participants. AE leading to discontinuation of study drug occurred in 10.7%, 5.4%, 6.3% of participants in the current triptan user, triptan-naïve, and TIR subgroups, respectively. The most common AEs leading to discontinuation were: dysgeusia, vomiting, increased alanine aminotransferase (ALT), and increased aspartate aminotransferase (AST) in the current triptan user subgroup (n=2 [1.7%] each); dysgeusia, migraine, increased ALT, and increased AST in the triptan-naïve subgroup (n=2 [0.8%] each); and dysgeusia (n=5 [2.1%]), throat irritation (n=4 [1.7%]), and nasal discomfort (n=3 [1.3%]) in the TIR subgroup.
Table 4.
On-Treatment AEs in the Long-Term Safety Analysis Set, According to Baseline Triptan Experience
| Current Triptan User (n=121) |
Triptan-Naïve (n=242) |
TIR (n=240) |
|
|---|---|---|---|
| Any AE | |||
| AE | 93 (76.9) | 179 (74.0) | 188 (78.3) |
| Severe AE | 8 (6.6) | 4 (1.7) | 10 (4.2) |
| Serious AEa | 0 | 3 (1.2) | 4 (1.7) |
| AE leading to discontinuation of study drug | 13 (10.7) | 13 (5.4) | 15 (6.3) |
| AE related to study drug | 71 (58.7) | 137 (56.6) | 134 (55.8) |
| SAE related to study drug | 0 | 0 | 0 |
| AE of special interest | |||
| Medication overuse headache AE | 0 | 0 | 0 |
| Hepatic-related AE | 3 (2.5) | 13 (5.4) | 7 (2.9) |
| Potential drug abuse AE | 11 (9.1) | 19 (7.9) | 14 (5.8) |
| Local irritation AEb | 60 (49.6) | 116 (47.9) | 123 (51.3) |
| CV AE | 0 | 0 | 0 |
| Suicidality AE | 0 | 0 | 0 |
| Preferred termsc | |||
| Dysgeusia | 50 (41.3) | 96 (39.7) | 90 (37.5) |
| Nasal discomfort | 11 (9.1) | 21 (8.7) | 30 (12.5) |
| COVID-19 | 4 (3.3) | 24 (9.9) | 17 (7.1) |
| Nausea | 4 (3.3) | 15 (6.2) | 18 (7.5) |
| Nasal congestion | 9 (7.4) | 13 (5.4) | 11 (4.6) |
| Throat irritation | 3 (2.5) | 10 (4.1) | 20 (8.3) |
| Back pain | 6 (5.0) | 11 (4.5) | 16 (6.7) |
| Myalgia | 9 (7.4) | 7 (2.9) | 7 (2.9) |
| Arthralgia | 6 (5.0) | 7 (2.9) | 8 (3.3) |
| Fatigue | 6 (5.0) | 5 (2.1) | 4 (1.7) |
| Taste disorder | 6 (5.0) | 5 (2.1) | 2 (0.8) |
| Procedural pain | 4 (3.3) | 1 (0.4) | 2 (0.8) |
| Rhinalgia | 2 (1.7) | 3 (1.2) | 3 (1.3) |
| Muscle strain | - | 4 (1.7) | 5 (2.1) |
| Injection site pain | 1 (0.8) | - | 2 (0.8) |
Notes: a Serious AEs included appendicitis, back pain, bile duct stenosis, concussion, fall, herpes zoster meningoencephalitis, multiple sclerosis, pleurisy, and pneumonia. b Includes dysgeusia. c Preferred terms with ≥5% participants in any group are shown.
Abbreviations: AE, adverse event; CV, cardiovascular; TIR, triptan insufficient responder.
Discussion
These analyses suggest that across efficacy endpoints, response rates generally favored zavegepant versus placebo for the acute treatment of migraine, and zavegepant was well tolerated, regardless of baseline triptan experience (current triptan user, triptan-naïve, or TIR). The findings of these pooled subgroup analyses of efficacy data from two trials are consistent with the overall results of each of those studies analyzed separately.21,22
In terms of safety outcomes, results from these analyses were consistent with the long-term safety trial where participants self-administered 1 dose/day as needed up to 8 times/month for up to 52 weeks to treat migraine attacks of any severity.28 The mean number of zavegepant doses self-administered per month was (3.1–3.3) doses/month.28 The most frequent AEs were dysgeusia and nasal discomfort.28 Dysgeusia and local nasal irritation have been reported across trials as the most common AEs of zavegepant nasal spray. These effects are generally mild-to-moderate, temporary, and usually resolve without treatment. Hepatic AEs were of particular interest and were monitored over the course of the 52 weeks of the long-term safety trial, with comparable rates of AST and ALT elevation across groups.28
Definitions of TIR vary somewhat among studies depending upon the nature of the study design and data available, among other factors.18,20,25 Approximately 30–40% of people have insufficient efficacy from or lack of tolerability to triptans for the acute treatment of migraine, according to a recent systematic review.18 Treatment recommendations for TIRs include trying other triptans, adding a nonsteroidal anti-inflammatory drug to the triptan, adding an anti-nausea drug, and trying a different drug class (e.g., gepant or ditan)14,15 Unfortunately, surveys and claims analyses suggest that when people do not refill their first triptan, treatment recommendations are not followed.20,29,30 Of those who fill an initial triptan prescription, more than half do not refill that prescription and fewer than 10% use two or more triptans over the course of a year. Other acute medications are used following an initial triptan prescription that is not refilled, often classes of drugs that are not recommended, particularly opioids and barbiturates.29,30
We explicitly acknowledge that TIR is heterogeneous and may be related to an inadequate initial response, recurrence, poor tolerability or other factors in various combinations. In this paper we show that zavegepant is effective in TIR. The majority of TIR used oral agents; the effectiveness of zavegepant in TIR may be due, in part, to difference in the mechanisms of gepants and triptans, or differences in route of administration between oral and non-oral therapy. As rimegepant and ubrogepant are also effective in TIR, differences in mechanism of action may be more important than differences in route of administration.25,31–33 Because nausea, vomiting, and gastric paresis can interfere with the effectiveness of oral agents, a subgroup of patients with migraine do better with non-oral therapy.34 Zavegepant is administered via nasal spray, thus circumventing issues surrounding oral absorption.
The current data suggest that zavegepant was effective for the acute treatment of migraine in the subgroup with a history of insufficient response to at least one triptan, with treatment differences versus placebo reaching statistical significance across all efficacy endpoints at 2 hours post-dose; these differences are nominal because the subgroup analyses were post hoc. The triptan-naïve subgroup had the lowest placebo-subtracted response rates due to high response rates observed with placebo. Of note, zavegepant was well tolerated in the subgroup with a history of insufficient response to one or more triptans when used for up to 1 year for the acute treatment of migraine.
These analyses have limitations, including their post hoc nature. Therefore, these findings should not be used to guide individualized treatment sequencing and strengthen the call for prospective, stratified comparative effectiveness trials in TIR populations. In the pooled efficacy analyses, the triptan-naïve group was slightly younger and more likely to be male and Hispanic, and less likely to have received preventive medication. In the long-term safety analyses, the triptan-naïve group was younger and more likely to be male, Black, or Hispanic. These baseline differences may confound contrasts across triptan experience groups. Finally, the randomized controlled trials that formed the basis of the pooled efficacy analysis set were not designed or powered to assess efficacy based upon triptan experience; a specifically designed study with prespecified analyses and a larger sample size is needed to better assess these post hoc results.
Conclusions
In these post hoc analyses and regardless of baseline triptan experience, response rates across efficacy endpoints generally favored zavegepant versus placebo for the acute treatment of migraine, and zavegepant was well tolerated.
Acknowledgments
Medical writing support was provided by Kim Russell, PhD, and Anne Marie McGonigal, PhD, CMPP, of Engage Scientific Solutions and was funded by Pfizer. These studies were sponsored by Biohaven, which was acquired by Pfizer in October 2022. Some of these data were presented at the 65th Annual Meeting of the American Headache Society (AHS), June 15–18, 2023, Austin, TX, USA. Some of these data were presented at the American Academy of Neurology (AAN), April 22–27, 2023, Boston, MA, USA.
Data Sharing Statement
Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.
Ethics/Ethical Approval
The studies in these post hoc analyses were conducted in accordance with the principles of the Guidelines for Good Clinical Practice, the Declaration of Helsinki, and all applicable local regulations. The protocols were approved by independent ethics committees and/or institutional review boards at each study center. Before any study-related procedures were undertaken, participants provided written informed consent. The studies were prospectively registered at ClinicalTrials.gov: NCT03872453, NCT04571060, and NCT04408794.21–23
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
Jelena M Pavlovic has received research support from National Institutes of Health and consultant/advisory board/honoraria from Allergan/AbbVie, Ipsen, Haleon, and Pfizer. Richard B Lipton has received research support from the National Institutes of Health, the US Food and Drug Administration, and the National Headache Foundation. He serves as consultant, advisory board member, or has received honoraria or research support from AbbVie/Allergan, Amgen, Axsome, Biohaven, Eli Lilly, GlaxoSmithKline, Lilly, Lundbeck, Merck, Novartis, Nuviebio, Teva, Vector, and Vedanta Research. He receives royalties from Wolff’s Headache, 8th edition (Oxford University Press, 2009), and Informa. He holds stock/options in Biohaven, CoolTech, and NuvieBio. Shivang Joshi has received consulting/speaking roles with Eli Lilly and Company, Amgen, AbbVie, Axsome, Impel, Lundbeck, Pfizer, and Teva. Robert Fountaine and Linda Mosher are employed by and own stock/stock options in Pfizer Inc. The authors report no other conflicts of interest in this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.