Evidence supports STS101 formulation for migraine treatment
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An intranasal dry powder formulation of dihydroergotamine, called STS101, outperformed other formulations of the drug for the treatment of migraine pain, according to researchers.
The findings were scheduled to be presented at the American Academy of Neurology Annual Meeting, which was canceled because of COVID-19.
STS101 (dihydroergotamine, Satsuma Pharmaceuticals) utilizes a dry-powder formulation that incorporates is a mucoadhesive drug carrier and engineered drug particle technologies, to achieve injectable-like characteristics, the drug’s manufacturer said.
John Kollins, president and CEO of Satsuma Pharmaceuticals, stated in an interview that STS101’s dry-powder formulation is “engineered with respect to excipients and tightly-controlled particle size to maximize deposition on the target tissue for drug absorption.” He added that the “poor solubility” of liquid dihydroergotamine (DHE) formulations limits the liquid medications’ ability to do what STS101 can.
Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, told Healio Primary Care that liquid nasal spray formulations of DHE have other limitations, suggesting a need for STS101’s mucoadhesive, dry-powder formulation.
“The nasal canal at the front of our noses prevents most liquids from reaching the point where the medicine would be optimally absorbed,” he said. “The nasal valve may also cause the medicine to puddle at the bottom of the nasal mucosa and go down the back of the throat.”
Researchers from Satsuma Pharmaceuticals performed a literature review to compare the pharmacokinetic profiles of STS101 and other DHE formulations, including the FDA-approved nasal spray Migranal (Bausch Health US) and the intravenously or intramuscularly administered DHE 45 (Novartis). Data from the developmental-stage liquid nasal spray INP104 Impel (Neuropharma) and the discontinued, orally inhaled, pulmonary routeMAP0004 were also included in their analysis.
The researchers found:
- STS101 had higher maximal concentration than Migranal and INP104.
- STS101 resulted in rapid and high drug exposure levels, similar to those achieved with DHE IM injection. By 30 minutes and at all timepoints thereafter, STS101 provided greater cumulative DHE exposure than MAP0004. STS101 showed more rapid drug absorption and greater drug exposure at all timepoints as compared with DHE liquid nasal spray products (INP104 and Migranal). By 2 hours after administration, drug exposure with STS101 was at least twofold higher than with MAP0004, INP104 and Migranal.
- STS101 provided DHE blood levels above the minimum effective concentration for approximately 2.5 hours, which was longer than the time MAP0004, INP104 or Migranal were at this same endpoint.
- Similar to MAP0004, STS101 demonstrated lower pharmacokinetic variability than Migranal and INP104.
Kollins added that STS101 has other properties that differentiate it from the more-commonly prescribed triptans.
“Dihydroergotamine can be administered anytime during the course of a migraine attack and there's minimal diminution of efficacy,” he said, adding that DHE reduces migraine recurrence better than triptans. Unlike triptans and other anti-migraine drugs, DHE is considered to have a low risk for causing medication overuse headache with frequent use and “is a standard treatment for medication overuse headache,” Kollins continued.
Tepper cautioned that physicians cannot predict the clinical effectiveness of STS101 based on pharmacokinetic data alone.
“Hence, in order to confirm that the STS101 pharmacokinetic data translate to a differentiated clinical efficacy profile, the FDA is requiring Satsuma Pharmaceuticals to conduct a randomized, placebo-controlled trial and a safety extension and tolerability trial, the former of which is underway,” Tepper noted.
According to Kollins, Satsuma Pharmaceuticals plans to submit a new drug application for STS101 by the end of 2021. He said it is too early to speculate on the cost of the drug. “But we're cognizant of the fact that cost-effective migraine treatment is one of the goals of treatment, as established in the American Headache Society treatment guidelines,” he added.
References:
DHE 45 [package insert]. East Hanover, New Jersey: Novartis; 2002.
FDA: Migraine: Development of drugs for acute treatment. Guidance for the industry. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/migraine-developing-drugs-acute-treatment. Accessed June 8, 2020.
Iwashima M. Water-insoluble Mucoadhesive Formulation Enables Consistent and Rapid Intranasal Absorption of Drugs, including Granisetron, Zolmitriptan and Dihydroergotamine. American Academy of Neurology Annual Meeting. April 25 – May 1, 2020 (meeting cancelled).
Migranal [package insert]. Bridgewater, NJ: Bausch Health US; 2019.
Strom S, et al. Pharmacokinetic comparison of STS101, an intranasal dry powder formulation of dihydroergotamine, with other intranasal, injectable and orally inhaled DHE formulations. American Academy of Neurology Annual Meeting. April 25 – May 1, 2020 (meeting cancelled).
Tepper SJ, et al. Mayo Clin Proc. 2011;doi:10.4065/mcp.2011.0093.
The ASCO Post. Pharmacokinetics and exposure response in drug development. https://www.ascopost.com/issues/february-25-2015/pharmacokinetics-and-exposure-response-in-drug-development/. Accessed June 8, 2020.