A phase 3 trial of Satsuma Pharmaceuticals’ acute treatment for migraine has missed its co-primary endpoints. The nasally administered formulation did no better than placebo, sending Satsuma’s stock down 76%.
STS101 is a dry-powder formulation of dihydroergotamine (DHE), an ergot derivative that has been used to treat migraines for decades. DHE is efficacious when given intravenously but cannot be given orally, leading researchers to formulate inhaled versions of the drug. Bausch Health sells a DHE nasal spray, Migranal, and other groups have tried to improve on its bioavailability and pharmacokinetics.
Satsuma emerged from phase 1 with evidence that STS101 has low pharmacokinetic variability, an issue with Migranal, and quickly gets DHE into the plasma. However, those early signs of promise have failed to translate into phase 3 success.
In a 1,140-subject phase 3, neither dose of STS101 was statistically better than placebo at granting migraine patients freedom from pain or their most bothersome symptom two hours after dosing. The inability of STS101 to move the needle against those measures caused the phase 3 to miss its co-primary endpoints.
Satsuma saw numerical differences in favor of both doses of STS101 at the two-hour point as well as statistically significant differences at time points from three hours onward. Those suggestions that the drug may work were too slight to stop investors from cratering the stock price of Satsuma, which is focused squarely on STS101.
Analysis of the phase 3 data is ongoing. The process may start to uncover why a candidate with an ingredient that is known to be active and, based on phase 1 data, looked to be bioavailable, failed to beat placebo.
The failure looks set to extend the wait for a new DHE formulation. MAP Pharmaceuticals developed an orally inhaled version of the drug, enabling it to land a $1 billion takeover by Allergan. MAP and Allergan submitted the drug for approval by the FDA three times. Each time, the FDA rejected the applications, in large part due to issues related to manufacturing and the delivery system.