STS101 nasal powder as a New treatment option for acute migraine with or without aura in adults

INTRODUCTION: Although effective acute migraine therapies exist, important gaps remain, particularly for patients whose nausea, vomiting, or delayed gastric emptying make oral medications unreliable. STS101 is a novel dihydroergotamine (DHE) nasal powder developed as a non-oral, single-use option for acute migraine treatment. AREAS COVERED: This profile evaluates the clinical use of STS101 as a non-oral DHE option for acute migraine and evaluates whether its formulation design, device characteristics, pharmacokinetics, clinical efficacy, and safety support a meaningful role in practice. A targeted PubMed and ClinicalTrials.gov search was performed from database inception throughout October 2025 using the keywords 'STS101,' 'dihydroergotamine,' 'migraine,' and 'intranasal powder.' Eligible sources included English-language clinical studies, trial registry records, regulatory documents, and relevant conference abstracts addressing STS101 formulation, pharmacokinetics, efficacy, safety, and/or regulatory development. Data from Phase 1 pharmacokinetic trials, the Phase 3 EMERGE and SUMMIT randomized controlled trials, and the ASCEND long-term safety study are discussed. EXPERT OPINION: STS101 is an intranasal DHE with more consistent absorption and lower pharmacokinetic variability than prior liquid intranasal DHE. Indeed, it may be useful for patients who require a non-oral rescue option, especially those who wish to avoid injections and those with gastrointestinal comorbidity or inadequate response to triptans or gepants. Cardiovascular contraindications remain important, and insurance policies may influence access. Its clinical role will likely depend on how clinicians weigh its delivery platform, DHE pharmacology, tolerability, and place relative to other available intranasal options. Comparative effectiveness trials with other intranasal therapies and real-world studies will be important for defining STS101's utilization in clinical practice.