The primary objective of ENDYMION is to assess the long-term safety and tolerability of soticlestat (TAK-935/OV935) in participants with developmental and epileptic encephalopathies (DEE); secondarily, to evaluate seizure frequency.

DEE is a heterogeneous group of rare highly-refractory epilepsies. Soticlestat is an inhibitor of cholesterol 24-hydroxylase that converts neuronal cholesterol to 24S-hydroxycholesterol (24HC), which is a positive allosteric modulator of NMDA receptors. Soticlestat may also reduce inflammation through glial modulation and neuroprotection.

ENDYMION is a prospective, multi-center, open-label extension study of soticlestat (up to 300 mg BID, oral) in participants with DEE who have participated in a previous soticlestat trial.

The majority of reported adverse events (abdominal pain, nausea, pyrexia, bronchial wall thickening, rales) were mild in severity, and no serious adverse events were observed. Median seizure frequency reduction was 46.4% following 13-24 weeks (n=7), 82% following 25-36 weeks (n=7), and 90% following 37-48 weeks (n=4) of treatment. The longest seizure-free consecutive duration by two different participants was 264 days (out of 350 treatment days) and 150 days (out of 336 treatment days), respectively.

In this small number of subjects in the open label ENDYMION study, soticlestat continues to show a favorable safety and tolerability profile, consistent with the previous Phase 2 TAK-935-2001 trial results in adult DEE.  A progressive reduction of seizure activity with longer duration of treatment is suggested by the data, although no definite conclusion can be drawn about open-label sustained efficacy due to the low number of subjects. But these data support the continued development of soticlestat for the treatment of epileptic encephalopathies.