Phase 3 Migraine Trial of DHE in Nasal Form Fails to Show Significant Difference

September 10, 2020

A formulation of dihydroergotamine (DHE) in a nasal powder form was no different than placebo for relief from pain and annoying symptoms at 2 hours post dose.

An effort to create a treatment for acute migraine pain out of a reformulated existing drug suffered a setback Thursday, as biopharmaceutical firm Satsuma Pharmaceuticals said a late-stage trial of its dihydroergotamine (DHE) nasal powder did not reach statistical significance.

In a statement, the company said the drug, STS101, was no different from placebo at either of the 2 co-primary end points: freedom from pain and relief of the most bothersome symptom (including photophobia, phonophobia, or nausea) at 2 hours post administration. The phase 3 trial, EMERGE, tested STS101 at 2 dosages: 3.9 mg and 5.2 mg.

The company said the drug was well tolerated, with no reports of serious adverse events and low adverse event rates. Topline data showed numerical differences vs placebo for both dosages, and the company said both dosages were significantly better than placebo at 3 hours post administration and at later times.

The president and CEO of Satsuma, John Kollins, said the firm was “surprised and disappointed” at the results and that the company would be continuing the analysis of trial data and considering its future business plans. Satsuma said it had cash, cash equivalents, and marketable securities of $93.7 million as of June 30, 2020.

The phase 3 EMERGE efficacy trial is a multicenter, single-dose, randomized, double-blind, placebo-controlled, parallel group US study with more than 1140 patients.

Participants were randomized (1:1:1) to receive 1 of 3 treatments: DHE 3.9 mg, DHE 5.2 mg, or matching placebo to use during their next migraine attack of at least moderate pain severity. The trial was statistically designed for greater than 99% power for the freedom-from-pain end point and greater than 95% power for the freedom-from-most-bothersome-symptom endpoint.

DHE is a derivative of ergotamine. A recent article called it “an older drug with an interesting history.” It is currently indicated for migraine in the United States via intravenous, intramuscular, and subcutaneous routes; it is also used in other countries in additional formulations. It was also the treatment for acute migraines before the development of triptans.