Takeda's Epilepsy Drug Fails in Consecutive Phase III Trials

Takeda announced on Monday disappointing results from two Phase III clinical trials of its investigational drug, soticlestat. The drug failed to achieve the primary efficacy endpoints in both the SKYLINE study for Dravet syndrome and the SKYWAY trial for Lennox-Gastaut syndrome.

The Japanese pharmaceutical company disclosed limited data, stating that in the SKYLINE study, soticlestat "narrowly missed" its primary goal. Although the drug candidate did show a reduction in convulsive seizure frequency compared to a placebo, this reduction did not reach statistical significance, with a p-value of 0.06.

Regarding secondary endpoints, soticlestat demonstrated "clinically meaningful" benefits in several areas. These included the responder rate and measures of seizure intensity and duration, as well as caregiver and clinician assessments of improvement. According to Takeda, these treatment effects were "nominally significant," with p-values all lower than or equal to 0.008.

The results were less promising in the Lennox-Gastaut syndrome trial. In this study, soticlestat did not significantly reduce the frequency of Major Motor Drop seizures, which was the primary outcome of the SKYWAY trial.

Despite these setbacks, the safety profile of soticlestat was consistent with previous findings, and the drug was generally well-tolerated in both trials.

“While we would have wished for more definitive results on the primary endpoints, we are encouraged by the positive outcomes seen in the totality of the data and are looking forward to engaging health authorities to determine the best path forward,” stated Sarah Sheikh, head of global development at Takeda.

Takeda is undertaking additional analyses of both studies and plans to present its final findings at an upcoming scientific meeting. The company also intends to collaborate with regulatory authorities to discuss the comprehensive data for soticlestat and to determine the best course of action moving forward.

In the meantime, Takeda will examine the financial implications of these Phase III trial outcomes on its first-quarter earnings for the period ending June 30.

Soticlestat is recognized for being a potent and highly selective inhibitor of the cholesterol 24-hydroxylase (CH24H) enzyme and has first-in-class potential. The CH24H enzyme plays a crucial role in maintaining brain cholesterol balance and affects glutamate signaling, which is linked to epilepsy and seizure propagation. Soticlestat works by normalizing the disrupted balance of excitatory and inhibitory signals in the brain.

Takeda acquired the global development and commercialization rights to soticlestat from Ovid Therapeutics in March 2021. The acquisition involved an upfront payment of $196 million, with potential additional payments of up to $660 million based on developmental, regulatory, and sales milestones. Moreover, Ovid is eligible for tiered royalties of up to 20% on soticlestat sales.

In a separate announcement on Monday, Ovid CEO Jeremy Levin remarked that the biotech company has utilized Takeda’s upfront payment from 2021 to develop an "exciting and differentiated pipeline," which is expected to generate multiple value-creating opportunities shortly.

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