Investigational Nasal Powder Rapidly Cuts Migraine Pain

SAN DIEGO — A single dose of a dihydroergotamine mesylate (DHE) nasal powder formulation appears to quickly and significantly reduce migraine pain, results of a new phase 3 study showed.

DHE is an acute treatment option for moderate or severe migraine attacks, with or without aura. It’s available as an injection, liquid nasal spray, or intravenous infusion.

The nasal powder (STS101; Satsuma Pharmaceuticals, Inc.) is an investigational DHE product that contains a mucoadhesive nasal powder formulation. It’s being studied for the acute treatment of migraines in adults.

“We found STS101 to be safe, well-tolerated, and easy to use,” study investigator Jessica Ailani, MD, director of MedStar Georgetown Headache Center and professor of clinical neurology, MedStar Georgetown University Hospital, Washington, DC, told Medscape Medical News.

The findings were presented on June 13 at the American Headache Society (AHS) Annual Meeting 2024.

A More Accessible Treatment?

Currently available DHE formulations are either not easy to obtain or not well-tolerated, said Ailani. “Bringing more treatment options to people with migraine is part of our mission at the Georgetown Headache Center.”

The product is delivered with a prefilled, single-use delivery device. “It’s simple to use; you just press the device, inhale, and the dose is dispensed,” said Ailani.

The advanced nasal powder and device technology maximizes the deposition of DHE on the nasal mucosa, which, the company reports, enhances DHE absorption, increases drug exposure, and reduces pharmacokinetic variability compared with DHE liquid nasal sprays.

The double-blind study (SUMMIT) included 1424 mostly White, female patients with a mean age of 38 years and a history of two to eight moderate or severe migraine attacks a month, with or without aura. To be eligible, participants also had to have had migraines for at least a year with onset before age 50.

The mean number of years since migraine onset among study participants was about 16.5, and about 10.2% were taking migraine prevention medication. The mean baseline six-item Headache Impact Test (HIT-6) score was just over 64.

The HIT-6 asks about headache pain severity and the impact of headaches on daily living and concentration.

Participants were randomly assigned to receive the DHE nasal powder or placebo. They self-administered a single 5.2-mg dose of the powder or placebo to treat one migraine attack of moderate to severe pain intensity.

Researchers assessed headache pain relief from 15 minutes through 48 hours post-dose using a four-point scale: No pain (0), mild pain (1), moderate pain (2), and severe pain (3). They defined pain relief as a reduction from moderate or severe pain to mild or no pain, with no prior use of rescue medication or a second dose of study medication.

The treated attacks had high rates of severe pain (38%), nausea (69%), photophobia (96%), phonophobia (91%), and allodynia (63%).

Relief in 2 Hours

The DHE powder demonstrated a statistically significant response rate for pain relief at 2 hours post-dose vs placebo (53.0% vs 44.6%; P < .01). It also significantly improved pain relief from 2 hours through 48 hours post-dose.

In those with baseline allodynia, the DHE powder had a higher response rate at 2 hours vs placebo (50.2% vs 43.5%; P < .05). This was similar to the response rate in participants without baseline allodynia (57.5% vs 46.6%; P < .05).

The product was effective at 2 hours post-dose in participants with menstruation-related migraine attacks (50.0% vs 39.6% for placebo) and in those without such attacks (50.0% vs 60.4%).

Researchers also looked at participants with severe headache impact (HIT-6 score, > 60). Here, they found a higher response rate for the powder than for the placebo at 2 hours post-dose (52.5% vs 42.8%; P < .001).

An additional analysis showed the DHE powder had significant effects vs placebo on photophobia, phonophobia, and nausea from 3 through 48 hours post-dose. This is noteworthy, as other routes of DHE administration have been related to an increase in nausea.

Study participants had a favorable response to the treatment. Most considered it easy to use and reported they would likely use it if available. In addition, compared with their usual migraine medications, study participants indicated STS101 worked faster and more consistently, and it enabled them to return to normal more rapidly.

Ailani said the research represents another step toward being able to offer a new treatment option to patients.

The nasal powder may be an ideal option for those who experience nausea with their migraine attacks, said Ailani. “This is also a particularly good option for someone who has tried a triptan and found it ineffective, or an individual who is experiencing longer attacks because DHE “can work early or late in an attack.”

Compelling Results

Commenting for Medscape Medical News, Rashmi B. Halker Singh, MD, associate professor of neurology at the Mayo Clinic in Phoenix, said the study results are “compelling.”

The novel nasal product should “fill a gap in our migraine treatment space,” she said. “We know that when an individual has allodynia, or is experiencing menstruation-related attacks, those migraine attacks can be associated with greater disability and are more resistant to treatment.”

These new data “likely speak not only to the DHE itself but also the ease of use of the novel delivery system as well as the consistency” of the outcomes, she added.

The study was funded by Satsuma Pharmaceuticals, Inc. Ailani reported she has been a consultant for Allergan/AbbVie, Amgen, Dr Reddy’ Laboratories, Eli Lilly, Eneura, GlaxoSmithKline, Gore, Ipsen, Linpharma, Lundbeck, Merz, Neurolief, Pfizer, Satsuma, Scilex Holding, and Theranica; has participated on a scientific advisory or data safety monitoring board for Allergan/AbbVie, Aeon, Eli Lilly, and Linpharma, Inc.; is an editor, associate editor, or editorial advisory board member of Current Pain and Headache Reports and Medscape Medical News; and has received research support from Ipsen, Parema, and Satsuma Pharmaceuticals, Inc. Halker Singh reported no relevant disclosures.