Data from the Phase 3 ASCEND trial indicates that STS101, a dihydroergotamine (DHE) nasal powder, is a safe and well-tolerated option for the acute treatment of migraine over a period of 12 to 18 months. The open-label study, led by Stewart J. Tepper, MD, FAHS, from The New England Institute for Neurology and Headache, assessed the long-term safety, tolerability, and efficacy of STS101 in adults aged 18-65 years experiencing 4 to 12 migraine attacks per month.
The study enrolled 344 participants with a history of migraine, with or without aura. Participants self-administered STS101 5.2 mg as needed, up to two doses within 24 hours and a maximum of 12 doses per month. Safety and tolerability were evaluated through physical and nasal examinations, vital signs, laboratory tests, and assessment of treatment-emergent adverse events (TEAEs).
Safety and Tolerability
Over the course of the study, participants experienced 6610 migraine attacks and used 8234 STS101 doses. Only 14.3% of doses were associated with a TEAE, with the majority being mild to moderate in severity. The most common adverse events included nasal discomfort (11.3%), dysgeusia (7.6%), nasal congestion (5.2%), nasopharyngitis (5.2%), and nausea (4.9%). Discontinuation due to adverse events was rare (4.4%).
"Notably, the incidence of local TEAEs was highest in the first 3-month period and decreased over time," the investigators wrote in their publication.
One serious TEAE, a non-ST-elevation myocardial infarction, occurred in a participant with a prior history of myocardial infarction who did not report contraindication for DHE use at baseline. The event was not considered life-threatening and was resolved.
The safety profile of STS101 was found to be comparable to that of dihydroergotamine nasal spray 1.45 mg, but with a lower incidence of adverse events.
Efficacy and Patient Satisfaction
STS101 provided rapid pain relief, with 36.6%, 67.1%, and 85.5% of treated attacks achieving pain relief at 2, 4, and 24 hours post-dose, respectively. Relief of the most bothersome symptoms was reported in 54.3%, 79.6%, and 91.3% of attacks at the same time points. Headache relief was achieved in 66.5%, 89.1%, and 94.3% of attacks.
Many participants rated STS101 as "good or very good" and "easy or very easy" to use at months 3, 6, and 12, and indicated they were very likely to use it again.
Study Limitations
The study's limitations include the lack of an active comparator, blinding, formal statistical analyses, and verification of self-reported aura rates. The investigators also acknowledged potential bias due to the long-term nature of the study, as participants who remained in the study were more likely to have had positive experiences with the medication. Additionally, some participants used earlier versions of STS101, which could have influenced their experiences.
Implications
Despite these limitations, the ASCEND trial provides evidence supporting the long-term safety and tolerability of STS101 for the acute treatment of migraine. While the FDA issued a complete response letter in January citing formulation concerns, these findings suggest that STS101 could be a valuable option for patients seeking a well-tolerated and effective migraine treatment. The study highlights the potential of STS101 to provide rapid and sustained relief from migraine symptoms with a favorable safety profile.
