Takeda reveals late-stage results for soticlestat in rare epileptic disorders

Takeda recently disclosed results from two advanced-stage trials of its investigational epilepsy drug, soticlestat (TAK-935). These trials, targeting Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), did not meet their primary endpoints but showed promising outcomes in several secondary measures.

Dravet syndrome and Lennox-Gastaut syndrome are rare forms of epilepsy, typically appearing in infancy or early childhood. These conditions are notoriously resistant to many existing anti-seizure treatments. In the United States, DS affects roughly one in every 15,000 to 21,000 individuals, while LGS is less common, impacting fewer than one in every 1,000 people.

The phase 3 SKYLINE trial tested soticlestat against a placebo, both administered alongside standard care, in patients with treatment-resistant DS. The study aimed to reduce convulsive seizure frequency but narrowly missed this primary goal. However, soticlestat did achieve "clinically meaningful and nominally significant" results in several key secondary endpoints. These included the responder rate, caregiver and clinician assessments of patient improvement, and measures of seizure intensity and duration over a 16-week treatment period.

Similarly, the phase 3 SKYWAY trial evaluated soticlestat in LGS patients, comparing it to a placebo in addition to standard care. This trial also failed to meet its primary endpoint, which was a reduction in major motor drop seizure frequency. Despite this, the drug was generally well tolerated and showed a safety profile consistent with earlier research.

Sarah Sheikh, who leads the neuroscience therapeutic area unit and global development at Takeda, expressed both disappointment and optimism. She acknowledged the persistent unmet needs for patients with developmental and epileptic encephalopathies like DS and LGS, despite current treatment options. "While we would have wished for more declarative results on the primary endpoints, we are encouraged by positive outcomes seen in the totality of the data," she remarked.

This update comes nearly four years after Takeda announced the phase 2 ELEKTRA study results. In that study, soticlestat met its primary endpoint by significantly reducing seizure frequency in children with DS or LGS.

Takeda plans to engage with regulatory authorities to discuss the comprehensive data from these studies and determine the next steps.