Zavzpret (zavegepant nasal spray) / Pfizer - LARVOL DELTA

Drugs for acute treatment of migraine. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • CNS Disorders • Migraine • Pain

Systemic administration of CGRP receptor antagonist alleviates neuropathic spontaneous pain in mice (Neuroscience 2026) - "Together, these findings identify CGRP signaling as a critical contributor to spontaneous pain after peripheral nerve injury and support further mechanistic studies. Clinically approved CGRP receptor antagonists (gepants; e.g., rimegepant, atogepant, ubrogepant, zavegepant) may therefore represent a promising therapeutic strategy for peripheral nerve injury-induced spontaneous pain."

Preclinical • CNS Disorders • Migraine • Pain

Physiologically Based Pharmacokinetic Modeling to Assess Transporter-Mediated Drug-Drug Interactions in Support of Labeling Recommendations for Zavegepant Nasal Spray. (PubMed, Clin Pharmacol Ther) - "In clinical drug-drug interaction (DDI) studies, oral zavegepant exposure increased in the presence of multiple-dose (MD) rifampin or itraconazole; however, no interaction was observed between intranasal (IN) zavegepant and itraconazole...Predicted IN zavegepant exposure change with SD cyclosporine A was 1.58-fold (AUCR) when assuming 90:10 proportion for OATP1B3:NTCP contribution to hepatic uptake. CYP3A inducers, carbamazepine and efavirenz, were predicted to have minimal effect on IN zavegepant PK. Overall, PBPK modeling and observed PK data support that CYP3A/P-gp inhibitors and inducers do not produce clinically relevant modulation in IN zavegepant plasma exposure; however, OATP1B3/NTCP inhibitors can significantly increase IN zavegepant exposure, and coadministration should be avoided."

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

Efficacy and Safety of Oral Zavegepant in Migraine Prevention: A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study in Patients with Chronic Migraine. (PubMed, Pain Ther) - P2/3 | "Oral zavegepant had a favorable safety and tolerability profile for up to 200 mg daily. Additional research is needed to determine the effectiveness of oral zavegepant as a preventive migraine treatment."

Clinical • Journal • P2/3 data • CNS Disorders • Migraine • Pain

Zavegepant Intranasal Spray for the Acute Treatment of Episodic Cluster Headache (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: The University of Texas Health Science Center, Houston

New P2 trial

Post Hoc Subgroup Analyses of the Efficacy and Safety of Zavegepant for the Acute Treatment of Migraine According to Baseline Triptan Experience. (PubMed, J Pain Res) - P2/3, P3 | "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."

Journal • Retrospective data • CNS Disorders • Migraine • Pain

Real-world outcomes of zavegepant use in a tertiary care setting using the Migraine Treatment Optimization Questionnaire-5. (PubMed, Headache) - "This study represents the first retrospective, real-world, patient-reported outcome study on the use of zavegepant using the validated MTOQ-5. These findings suggest that intranasal zavegepant may be a useful acute migraine treatment option in clinical practice, with patient-reported improvement in pain, most bothersome symptom, function, tolerability, and willingness to reuse. However, the descriptive single-arm design and exclusion of single dose or nonusers limit interpretation and preclude comparative conclusions. Further real-world follow up with larger sample sizes is warranted to validate these findings."

Journal • Real-world evidence • CNS Disorders • Migraine • Pain

Patient Experience with 10 mg Intranasally Administered Zavegepant as an Acute Treatment of Migraine Attacks: Qualitative Research Findings. (PubMed, Neurol Ther) - "Overall, zavegepant 10 mg IN was perceived as an effective and fast-acting acute treatment for migraine attacks. Although side effects such as dysgeusia may delay or reduce use in some patients, most value zavegepant's effectiveness and functional benefits. These findings underscore the need for improved patient education on administration techniques and side effects to optimize real-world outcomes."

Journal • CNS Disorders • Migraine • Pain

Safety Profile of Zavegepant in the Treatment of Acute Migraine: Insights from the FDA Adverse Event Monitoring System Database. (PubMed, Pharmaceuticals (Basel)) - " These results suggest a safety profile for zavegepant consistent with previous knowledge regarding CGRP-RAs. However, nasal and/or oropharyngeal AEs, plausibly related to intranasal exposure, may affect perceived tolerability and timely use, warranting further investigation."

Adverse events • Journal • CNS Disorders • Cough • Migraine • Pain • Respiratory Diseases

A phase 3, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of zavegepant for the acute treatment of migraine in Asian adults (AHS 2026) - P3 | "This study demonstrated a positive benefit-risk profile for zavegepant versus placebo in the acute treatment of migraine in Asian adults. Statistically significant efficacy was observed for both co-primary endpoints, and 6 of the 8 key secondary endpoints, including significant evidence of rapid onset of pain relief and durability of response. Zavegepant was well tolerated in Asian adults with migraine and demonstrated a favorable safety profile."

Clinical • P3 data • CNS Disorders • Migraine • Pain

Efficacy and safety of zavegepant for the acute treatment of migraine: pooled analysis of two phase 3 randomized controlled trials (AHS 2026) - No abstract available

P3 data • Retrospective data • CNS Disorders • Migraine • Pain

The impact of ubrogepant on the use of other migraine acute treatments, opioid discontinuation, and healthcare utilization: Results from a pre-post opioid subcohort analysis (AHS 2026) - "Acute medications other than ubrogepant included acetaminophen, almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan, dihydroergotamine, ergotamine, amobarbital, aprobarbital, butabarbital, butalbital, mephobarbital, metharbital, pentobarbital, phenobarbital, secobarbital, talbutal, barbital, codeine, hydrocodone, meperidine, morphine, oxycodone, propoxyphene, tramadol, aspirin, bromfenac, celecoxib, diclofenac, diflunisal, esomeprazole, etodolac, famotidine, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, meclofenamate, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, sulindac, tolmetin, lasmiditan, Zavegepant, and Rimegepant (<15 pills). Opioid use included acetaminophen/tramadol, oxymorphone, levorphanol, buprenorphine/naloxone, meperidine, morphine, oxycodone, codeine, methadone, oxycodone, hydromorphone, butorphanol, and tapentadol... In patients with a history of opioid use,..."

HEOR • CNS Disorders • Migraine • Pain

Comparison of FDA approved intranasal acute migraine treatment adverse event profiles (AHS 2026) - "One Sentence Summary: STS101 (dihydroergotamine nasal powder) shows a low rate of local adverse events in its approved prescribing information as compared with other approved intranasal acute migraine treatments...Prescribing information dates reviewed were ATZUMI (April 2025), Migranal (September 2022), Trudhesa (May 2022), Zavzpret (August 2025), Imitrex nasal spray (December 2025), and Zomig nasal spray (May 2019)... Nasally administered products for the acute treatment of migraine are generally well tolerated. STS101 shows a favorable adverse event profile in long term prn use as compared with other FDA-approved intranasal acute migraine treatments. Most commonly reported adverse events (≥5% and occurring more frequently than placebo) as listed in the U.S. prescribing information for FDA-approved intranasal acute migraine treatments."

Adverse events • CNS Disorders • Migraine • Pain

Comparative efficacy of Symbravo® versus gepants for acute treatment of migraine: A network meta-analysis (AHS 2026) - "Background: Symbravo® (20 mg MoSEIC(TM) meloxicam and 10 mg rizatriptan [MxRz]) is a novel, oral, rapidly absorbed, multi-mechanistic investigational medicine approved for acute treatment of migraine with or without aura. The NMA favors MxRz over rimegepant, ubrogepant, and zavegepant for acute migraine. MxRz is particularly effective in achieving 2-h and 2–24 h sustained pain freedom, offering a promising therapeutic alternative for patients with inadequate response to prior treatments."

Retrospective data • CNS Disorders • Migraine • Pain

Primary care providers and gepant prescription: Barriers and opportunities for expanding access to migraine treatment (AHS 2026) - "Rimegepant was most frequently prescribed (59%), followed by ubrogepant (37%), atogepant (4%), and zavegepant (0%). At this tertiary academic center, headache specialists prescribe the majority of gepants, with PCPs accounting for approximately one-fifth of total prescriptions despite managing most patients with migraine. Significant discomfort exists among PCPs regarding gepant prescribing, even among those with prior prescribing experience. Key barriers—education gaps, prior authorization burden, and cost awareness—represent modifiable targets for intervention."

Clinical • CNS Disorders • Migraine • Pain

The pharmacology of gepants in migraine: A scoping review on mechanisms, clinical applications, and combination strategies. (PubMed, Headache) - "Gepants represent an effective and well-tolerated class of CGRP-targeted therapies with flexible use in acute and preventive migraine management. Their pharmacological properties support individualized treatment strategies and potential combination approaches; however, long-term safety, optimal positioning, and the efficacy of combination regimens require further investigation."

Journal • Review • Cardiovascular • CNS Disorders • Hepatology • Liver Failure • Migraine • Pain

Quality by design based development and optimization of a thermoreversible in situ intranasal gel of zavegepant for nose to brain delivery in migraine therapy. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Nine formulations (VF1-VF9) were developed and evaluated for physicochemical properties, gelation behavior, mucoadhesion, in-vitro drug release, ex vivo permeation, and in vivo anti-migraine efficacy using a nitroglycerin-induced migraine model in rats...In vivo studies demonstrated significant improvement in locomotor activity, photophobia, and mechanical allodynia, with biochemical normalization of CGRP (41.16 pg/mg), MDA, NO, GSH, and SOD levels, comparable to sumatriptan...The optimized thermosensitive nasal gel (VF2) of Zavegepant presents a promising, non-invasive strategy for acute migraine therapy with sustained drug release, enhanced mucosal retention, and putative CNS delivery via olfactory and trigeminal pathway. Its clinical potential lies in offering fast, localized treatment with fewer systemic side effects and improved patient compliance."

Journal • CNS Disorders • Migraine • Pain

Knowledge Discovery and Drug-Repurposing Framework for Pancreatic Ductal Adenocarcinoma: Molecular Networking and Computational Docking. (PubMed, Comput Struct Biotechnol J) - "These proteins exhibited high-affinity interactions with zavegepant (a clinically approved CGRP receptor antagonist), omilancor, bemcentinib, conivaptan, and APTO-253...Thus, we suggest a systems-level platform for nominating ligandable PDAC targets and clinically actionable compounds. The framework highlights opportunities for rational drug repurposing and motivates future mechanistic studies at the intersection of proteomics and structure-based screening for targets to PDAC."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • AHNAK2 • ANXA2 • EIF2A • EIF2S1

Risk Stratification of Hypertension Induced by CGRP Antagonist in Migraine Treatment: A Retrospective Observational Analysis (AAN 2026) - "Design/Methods 250 patients prescribed any CGRP antagonist, including erenumab, fremanezumab, galcanezumab, eptinezumab, and the gepants (ubrogepant, rimegepant, atogepant, zavegepant).Variables extracted included: age at start, sex, and body mass index (BMI). Comorbidities: pre-existing hypertension, diabetes, chronic kidney disease, stroke, and obstructive sleep apnea (OSA); OSA treatment status (treated vs untreated) was noted. Conclusions Hypertension following CGRP initiation is an early event, occurring within the first few months.Once developed, hypertension tends to persist, with no new cases after 3 months. The pattern is similar across drug classes, indicating that risk is likely related to the CGRP pathway blockade rather than a specific molecule."

Retrospective data • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Diabetes • Hypertension • Metabolic Disorders • Migraine • Nephrology • Obstructive Sleep Apnea • Pain • Renal Disease • Respiratory Diseases • Sleep Disorder

Network Meta-analysis of Atzumi (STS101) Dihydroergotamine Nasal Powder Versus Modern Oral and Intranasal Agents for the Acute Treatment of Migraine (AAN 2026) - "In contrast, zavegepant 10 mg IN, ubrogepant 50 mg PO, and rimegepant 75 mg ODT achieved PF RRs of 1.49, 1.52, and 1.46, respectively, while sumatriptan 100 mg PO remained highest (1.88 [1.64–2.15]). Safety favored Atzumi, with mild nasal discomfort (8.3%) and dysgeusia (3.7%), and no serious adverse events, compared with higher systemic AEs for oral triptans. Conclusions Atzumi (STS101) showed sustained efficacy beyond 3 hours with excellent tolerability, offering a safe non-oral option for acute migraine; overall study quality was high with low ROB 2.0."

Retrospective data • CNS Disorders • Migraine • Pain

Post-marketing safety of CGRP monoclonal antibodies and gepants: A systematic review of spontaneous reporting system data. (PubMed, Headache) - "This systematic review confirms that CGRP inhibitors have a manageable yet complex safety profile. It distinguishes rare, serious cerebrovascular events (RCVS, CeAD) associated with some mAbs but not with gepants, as well as shared adverse effects such as Raynaud's phenomenon and alopecia. Significant heterogeneity in safety profiles-from erenumab's pronounced constipation SDR to zavegepant's unique dysgeusia-challenges the view of CGRP inhibitors as a monolithic category. These findings provide a clear rationale for personalized risk assessment, enabling clinicians to tailor treatment to individual patient profiles."

Journal • P4 data • Review • Alopecia • Cardiovascular • CNS Disorders • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Immunology • Migraine • Pain • Rheumatology • Vascular Neurology • ROR1

Early Experience Treating Vestibular Migraine With Small Molecule CGRP Antagonists. (PubMed, Otolaryngol Head Neck Surg) - "Gepants are well-tolerated by patients and are promising agents for the treatment of vestibular migraine."

Journal • CNS Disorders • Migraine • Otorhinolaryngology • Pain • Vertigo

Integrating gepants into clinical practice for the acute treatment of migraine. (PubMed, Headache) - "Key advantages of gepants include their favorable tolerability, efficacy for the acute treatment of both the prodromal/premonitory phase (ubrogepant) and the headache phase of migraine (ubrogepant, rimegepant, zavegepant), lack of cardiovascular contraindications, and lack of association with medication-overuse headache. Disadvantages include limitations due to cost and access and CYP3A4 drug interactions for most gepants. Together, the advantages may help to optimize patient care and lead to better persistence and effectiveness in a real-world setting. Head-to-head studies are needed to clarify the comparative effectiveness of triptans and gepants."

Journal • Review • Cardiovascular • CNS Disorders • Migraine • Pain • CYP3A4

Zavegepant and lactation: What the pharmacokinetic data suggests. (PubMed, Headache) - No abstract available

Journal • PK/PD data • CNS Disorders • Migraine • Pain • Pediatrics • Women's Health

Safety analysis of gepants for migraine treatment: A pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) database. (PubMed, Headache) - "Gepants display distinct AE profiles, with oral agents linked to gastrointestinal and neurological effects and intranasal zavegepant associated with respiratory irritation. Continued post-marketing surveillance is essential to inform personalized migraine management and guide future CGRP-targeted drug development."

Adverse events • Journal • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Migraine • Pain