ARCADE is a Phase 2 open-label, signal-finding pilot study designed to inform the potential for future development of soticlestat in CDD and Dup15q. The study enrolled 20 patients, ages 2 to 55 years, with refractory epileptic seizures associated with CDD (n=12) or Dup15q (n=8) and consisted of a four- to six-week screening period to establish baseline seizure frequency, followed by a 20-week treatment period, including an eight-week titration/dose optimization period and a 12-week maintenance period. Patients in the study were allowed to be on one to six concomitant anti-epileptic drugs (AEDs), with the majority of patients concomitantly treated with at least four AEDs, representing a highly refractory patient population. The primary objective of the ARCADE study was to determine percent change from baseline in motor seizure frequency during the 12-week maintenance period. Afterward, patients were offered the chance to continue soticlestat treatment in the ENDYMION open-label extension study, and all patients who completed ARCADE elected to roll over into ENDYMION.
Data from Dup15q Syndrome
Dup15q patients also exhibited a variety of seizures types, including motor (tonic and atonic), myoclonic and absence seizures. In Dup15q patients (n=8), there was an increase in median motor seizure frequency of 13% during the 20-week study period (eight-week dose titration and 12-week maintenance period) and an increase of 12% during the 12-week maintenance period (primary objective of the study). However, longer-term data from the four Dup15q patients who reached nine months of continuous treatment with soticlestat in ENDYMION showed a 74% reduction in median motor seizure frequency. Individual Dup15 patients demonstrated improvements in other seizure types, as reported previously.
In addition, 38% of Dup15q patients were deemed markedly improved with minimal or no adverse events on the CGI-C scale after starting soticlestat treatment. For the Care-GI-C scale, 50% (in 4/8 patients) of caregivers reported improvement on soticlestat treatment at the end of the ARCADE study. Exit interviews from the caregiver for the ARCADE study Dup15 cohort also show similar improvements to the CDD patients in the study.