Takeda has axed plans to seek approval for its failed epilepsy drug candidate soticlestat. The Japanese drugmaker pulled the plug on the program after the FDA pointed out the shortcomings of its clinical data package.
Soticlestat, a cholesterol 24 hydroxylase inhibitor, failed phase 3 trials in two forms of epilepsy last year. The studies showed the molecule was statistically no better than placebo at reducing the frequency of seizures in people with Lennox-Gastaut syndrome (LGS) and Dravet syndrome. Takeda soon removed the LGS program from its pipeline and reported a $140 million charge related to the molecule.
Yet, Takeda noted the “totality of the data”—a favorite phrase of sponsors of failed trials—to make the case soticlestat had a future in Dravet. The FDA quashed Takeda’s hopes. According to Takeda, the U.S. regulator said the current data is incapable of showing substantial evidence of effectiveness in Dravet.
Takeda uploaded the phase 3 data to ClinicalTrials.gov late last year. The update shows Dravet patients on soticlestat experienced a 22.16% reduction in convulsive seizure frequency per 28 days, compared to an 8.64% reduction in the placebo group. The difference fell short of statistical significance, yielding a p-value of 0.061.
Takeda linked the drug candidate to nominally significant changes on six secondary endpoints, tracking positive shifts in responder rate, measures of caregiver and clinician global impression of improvement, and seizure intensity and duration scales over the 16-week treatment period. Coupled with the relatively narrow miss on the primary endpoint, Takeda thought the secondary measures could get it over the line.
The company’s inability to convince the FDA of the strength of the data package has implications for Ovid Therapeutics and Ligand Pharmaceuticals. Ovid inked a deal with Takeda in 2021 and sold part of its royalty rights to Ligand in 2023. The failure of the phase 3 soticlestat trials sparked changes at Ovid, which would have been in line for milestones and royalties if the molecule had come to market.
The removal of soticlestat wasn't the only change that Takeda revealed today. The company also announced that Julie Kim, president of Takeda’s U.S. Business Unit, will take over from CEO Christophe Weber when Weber retires in June 2026.