Zavzpret (zavegepant nasal spray) / Pfizer - LARVOL DELTA

Head-to-head relief: ubrogepant, rimegepant, and zavegepant in migraine treatment. (PubMed, Pain Manag) - "The NNT values for achieving pain freedom at two hours were 9 for rimegepant, 11 for zavegepant, and 12 for ubrogepant, which are comparable to NSAIDs such as naproxen (NNT = 11). Triptans demonstrated lower NNTs, indicating higher efficacy. Gepants offer effective, well-tolerated alternatives with no significant cardiovascular risk and minimal potential for medication-overuse headache."

Head-to-Head • Journal • Review • Cardiovascular • CNS Disorders • Migraine • Pain

A Study to Learn About Zavegepant as the Acute Treatment of Migraine in Asian Adults (clinicaltrials.gov) - P3 | N=1238 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Migraine • Pain

Cost-effectiveness Analysis of Zavegepant in Acute Migraine Treatment (ISPOR 2025) - "Zavegepant is cost-effective compared with rimegepant for the acute treatment of migraine under the threshold of $100,000 per QALY gained."

Cost effectiveness • HEOR • CNS Disorders • Migraine • Pain

The efficacy and safety of zavegepant nasal inhalation versus oral calcitonin-gene related peptide receptor antagonists in the acute treatment of migraine: a systematic review and network meta-analysis of the literature. (PubMed, J Headache Pain) - "Zavegepant 10 mg can quickly relieve symptoms and has no significant difference in safety compared with oral drugs, which can provide rapid and safe efficacy in the acute treatment of migraine. However, compared with other oral CGRP receptor antagonists, zavegepant 10 mg by nasal inhalation has no obvious advantage in long-term symptom relief rate."

Clinical • Journal • Retrospective data • Review • CNS Disorders • Migraine • Pain

Comparative Efficacy of AXS-07 vs. Gepants for Acute Treatment of Migraine: A Network Meta-Analysis (AAN 2025) - "The NMA favors AXS-07 over rimegepant, ubrogepant, and zavegepant for acute migraine. AXS-07 is particularly effective in achieving 2-hour and 2-24 hour sustained pain freedom, offering a promising therapeutic alternative for patients with inadequate response to prior treatments."

Retrospective data • CNS Disorders • Migraine • Pain

Health Technology Assessment: Evaluation of 8 CGRP-Targeted Therapy Drugs for the Treatment of Migraine. (PubMed, Drug Des Devel Ther) - "The final assessment result scores from highest to lowest were rimegepant (84.5 points), erenumab (75.78 points), galcanezumab (74.02 points), fremanezumab (73.93 points), atogepant (72.64 points), eptinezumab (71.69 points), ubrogepant (70.37 points), zavegepant (56.44 points). Rimegepant, erenumab, fremanezumab, atogepant, galcanezumab, eptinezumab, ubrogepant can be entered into the medication list of medical institutions as strongly recommended drugs."

Journal • Review • CNS Disorders • Migraine • Pain

Deconvoluting zavegepant drug-drug interactions: A phase I study to evaluate the effects of rifampin and itraconazole on zavegepant pharmacokinetics. (PubMed, Clin Transl Sci) - "This Phase I, open-label, fixed-sequence study evaluated the effects of itraconazole (a strong cytochrome P450 3A4 [CYP3A4] and P-glycoprotein [P-gp] inhibitor) on the pharmacokinetics of intranasal/oral zavegepant and the effects of rifampin (a strong inducer of CYP3A4 and P-gp; and an inhibitor of organic anion transporting polypeptide 1B3 [OATP1B3]) on oral zavegepant in healthy participants. These results suggest that OATP1B3 and intestinal P-gp are the more prominent pathways, as opposed to CYP3A4, for a zavegepant drug-drug interaction. Coadministration of OATP1B3 inhibitors with zavegepant nasal spray should be avoided."

Journal • P1 data • PK/PD data • CNS Disorders • Migraine • Pain • CYP3A4

Effects of multiple-dose administration of zavegepant nasal spray on the single-dose pharmacokinetics of ethinyl estradiol-levonorgestrel. (PubMed, Headache) - "Co-administration of zavegepant nasal spray with a single dose of an oral contraceptive resulted in no clinically meaningful changes (<12% increase) in EE-LNG exposure."

Journal • PK/PD data • CNS Disorders • Migraine • Pain

Sex/Gender Equity Considerations in Clinical Trials of Gepants for Migraine: A Systematic Review (ISPOR-EU 2024) - " We identified 17 unique trials of the following: rimegepant (6 RCTs), atogepant (5 RCTs), ubrogepant (4 RCTs), and zavegepant (2 RCTs). Despite the well-established gendered nature of disease and high proportions of women recruited, gepants trials for migraine did not appear to fulfil sex/gender health equity considerations in study design, conduct, analysis, and reporting. This oversight may affect the health technology assessment process leading to potential biases and inequities in healthcare recommendations and policies."

Clinical • Review • CNS Disorders • Migraine • Pain

Population pharmacokinetic modeling of zavegepant, a calcitonin gene-related peptide receptor antagonist, in healthy adults and patients with migraine. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Age (range 18-71 years), race, ethnicity, sex, renal function, and co-administration of oral contraceptives or sumatriptan did not significantly change zavegepant pharmacokinetics. Moderate hepatic impairment (Child-Pugh score 7-9) or co-administration of rifampin decreased elimination clearance of oral zavegepant by ~40%. The zavegepant population pharmacokinetic model adequately characterized zavegepant concentration-time profiles, the bioavailability of intranasal and oral zavegepant, as well as the effect of intrinsic and extrinsic factors on zavegepant pharmacokinetics."

Journal • PK/PD data • CNS Disorders • Hepatology • Migraine • Pain

Implications of trinodal inhibitions and drug repurposing in MAPK pathway: A putative remedy for breast cancer. (PubMed, Comput Biol Chem) - "Additionally, a total of 1867 repurposed analgesic, antibiotic, and antiparasitic drugs, including Zavegepant (-13.399 kcal/mol for PDPK1), Adozelesin (-11.74 kcal/mol for mTOR) and Modoflaner (-11.29 kcal/mol for PDPK1), showed promising binding energetics while targeting our triad points than other compounds used. This approach prompts for mitigating not only breast cancer but other elusive diseases as well, with state-of-the-art multitargeted therapies coupled with bioinformatic strategies."

Journal • Breast Cancer • Oncology • Pain • Solid Tumor • mTOR • PDPK1

A Study to Learn How the Study Medicine Called Zavegepant is Taken Up Into Blood and Breast Milk of Healthy Breast-Feeding Women (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Pfizer | Recruiting ➔ Completed | Trial completion date: Feb 2025 ➔ Sep 2024 | Trial primary completion date: Feb 2025 ➔ Sep 2024

Trial completion • Trial completion date • Trial primary completion date

A Study to Learn About Zavegepant as a Treatment for Multiple Migraine Attacks in Adult Participants (clinicaltrials.gov) - P3 | N=1280 | Not yet recruiting | Sponsor: Pfizer | Trial completion date: Feb 2027 ➔ Aug 2027 | Trial primary completion date: Feb 2027 ➔ Aug 2027

Trial completion date • Trial primary completion date • CNS Disorders • Migraine • Pain

Assessment of pharmacokinetic and pharmacodynamic interactions between zavegepant and sumatriptan: A phase 1, randomized, placebo-controlled study in healthy adults. (PubMed, Headache) - "Coadministration of zavegepant with sumatriptan was safe and without PD or PK interactions in healthy adults."

Journal • P1 data • PK/PD data • CNS Disorders • Migraine • Pain

Mass balance and pharmacokinetic characterization of zavegepant in healthy male subjects. (PubMed, Clin Transl Sci) - "A single IV infusion of 5 mg [14C]-zavegepant was well tolerated in healthy male subjects. Disposition findings of IV [14C]-zavegepant are applicable to the disposition of the approved zavegepant nasal spray."

Journal • PK/PD data • CNS Disorders • Migraine • Pain

The influence of pharmacodynamics and pharmacokinetics on the antimigraine efficacy and safety of novel anti-CGRPergic pharmacotherapies: a narrative review. (PubMed, Expert Opin Drug Metab Toxicol) - "The existence of patients with medication-resistant migraine may be due to the: (i) complex migraine pathophysiology, in which several systems appear to be deregulated before, during, and after a migraine attack; and (ii) pharmacodynamic and pharmacokinetic properties of antimigraine medications. As envisioned here, although seminal studies support the notion that CGRP plays a key role in migraine headache, the dysfunction of CGRPergic transmission does not seem to be relevant in all cases."

Journal • PK/PD data • Review • CNS Disorders • Migraine • Pain

Intranasal zavegepant for the acute treatment of migraine. (PubMed, Expert Rev Neurother) - "Dysgeusia was common; future studies are needed to better characterize this adverse event. Head-to-head studies are lacking with other migraine-specific therapies; the decision to treat should be patient-centered, with attack-specific characteristics in mind."

Clinical • Journal • Review • Cardiovascular • CNS Disorders • Migraine • Pain

Long-term safety of zavegepant nasal spray for the acute treatment of migraine: A phase 2/3 open-label study. (PubMed, Cephalalgia) - P2/3 | "One year of zavegepant 10 mg nasal spray up to eight times per month was safe and well tolerated.Trial registration: Clinicaltrials.gov: NCT04408794."

Journal • P2/3 data • Back Pain • CNS Disorders • Infectious Disease • Migraine • Musculoskeletal Pain • Novel Coronavirus Disease • Pain

Comparison of gepant effects at therapeutic plasma concentrations: connecting pharmacodynamics and pharmacokinetics. (PubMed, J Headache Pain) - "The relatively low predicted potency of zavegepant to inhibit CGRP-induced relaxation at therapeutic systemic plasma concentrations may point to the relevance of local delivery to the trigeminovascular system through intranasal administration. This approach may have additional benefits for various groups of patients, including overweight patients."

Clinical • Journal • PK/PD data • CNS Disorders • Migraine • Obesity • Pain

Effectiveness and Tolerability of Zavegepant for Acute Migraine Treatment Among Those Using CGRP Targeting Preventive Medications (clinicaltrials.gov) - P4 | N=200 | Recruiting | Sponsor: Mayo Clinic | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2024 ➔ Mar 2024

Enrollment open • Trial initiation date • CNS Disorders • Migraine • Pain

Reduced hepatic impairment study to evaluate pharmacokinetics and safety of zavegepant and to inform dosing recommendation for hepatic impairment. (PubMed, Clin Transl Sci) - "One treatment-emergent adverse event (mild, treatment-related headache) was reported in a participant with normal hepatic function. No dosage adjustment of intranasal zavegepant is required in adults with mild or moderate hepatic impairment."

Journal • PK/PD data • CNS Disorders • Hepatology • Migraine • Pain

A Study to Learn How the Study Medicine Called Zavegepant is Taken Up Into Blood and Breast Milk of Healthy Breast-Feeding Women (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open

Examining return to normal function trajectories, a post-hoc analysis of Zavegepant (AHS 2024) - P2/3 | "Return to normal function is a patient-centric outcome that is linked to quality-of-life and impact of migraine on daily living. In this post-hoc analysis, zavegepant was associated with rapid and sustained return to function compared to placebo, resulting in more time spent with normal functioning over the 48-h study period. Reduced pain severity and the absence of nausea, photophobia, and phonophobia were predictors of better functioning."

Retrospective data • CNS Disorders • Migraine • Pain

Long-term safety of zavegepant nasal spray for the acute treatment of migraine in adults with a history of anxiety and/or depression and in adults with concomitant use of antidepressants (AHS 2024) - P2/3 | "Zavegepant nasal spray, up to 8 doses per month for up to 52 weeks, was well tolerated and had a favorable safety profile for the acute treatment of migraine in adults with a history of anxiety and/or depression and in adults with migraine using concomitant antidepressants."

Clinical • Back Pain • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Migraine • Mood Disorders • Musculoskeletal Pain • Pain • Psychiatry • Sleep Disorder

Efficacy and safety of zavegepant for the acute treatment of migraine in Black/African American adults: Results from 2 randomized, placebo-controlled clinical trials (AHS 2024) - P2/3, P3 | "The benefits of zavegepant 10 mg for the acute treatment of migraine in Black/African American adults were generally comparable to the overall population."

Clinical • CNS Disorders • Migraine • Pain