Dry Powder Formulation of Dihydroergotamine Adheres to Nasal Lining and Safely Treats Migraine 

In the ASCEND (NCT04406649) safety and tolerability study, a novel dry powder formulation of dihydroergotamine (DHE) (STS101; Satsuma Pharmaceuticals, South San Francisco, CA) was found safe and tolerable for use as an acute treatment for episodic migraine.  

Treatment-emergent events occurred in 33.9% of participants (n=271), 85% of which were nasal symptoms, and in 8.3% of attacks (n=5,443), 88% of which were nasal events. A second dose was used in 19.4% of attacks. 

Overall, adverse events occurred in 55% of participants and 10.7% of attacks. The most frequent adverse events (% attack; % participants) were nasal discomfort (3.3%; 15.1%), dysgeusia (3.2%; 8.1%), nasal congestion (1.7%; 5.9%), nausea (0.3%, 4.4%), rhinorrhea (0.8%; 3.3%), vomiting (0.2%; 3.3%), nasal pain (0.2%; 3.0%), and migraine (0.2%; 2.6%). 

All participants used the treatment at least once, and 61.2% discontinued treatment; 23% had fewer than 2 migraine attacks/month after enrollment, 22% withdrew consent or were lost to follow-up, and 8.1% discontinued due to adverse events.

Of the 22 discontinuations due to adverse events, 20 were treatment related, which included nasal symptoms; vomiting, worsening of migraine, upper gum pain, and leg or abdominal pain. The other 2 discontinuations, considered unrelated to treatment, were a case of postural orthostatic tachycardia (POTS) and a case of Cushing disease. Of note, after the data cutoff for this analysis, a participant discontinued treatment due to a treatment-related nonST-elevation myocardial infarction; they had not reported pre-existing cardiovascular risk factors.

This novel formulation of DHE is an engineered mucoadhesive nasal powder designed for the delivery of DHE that delivers a dose of 5.2 mg and can be used up to twice every 24 hours. Delivery of drug is via delivered with a single-use nasal delivery device, which delivers a full dose with a single squeeze within seconds. 

In the ASCEND trial, participants, age 18 to 65 with at least a 1-year history of migraine and no more than 1 cardiovascular risk factor, treat migraine are treating migraine attacks acutely with this DHE formulation. Up to 12 doses/month can be used for up to a year, and participants are having 11 study visits during the study. Participants are limited to using no more than 2 other drugs to treat migraine.