Positive Impacts on Non-Seizure Symptoms, Caregiver Experience Observed With Soticlestat

Author(s):

Using a caregiver questionnaire, noted improvements in verbal, non-verbal communication, and engagement were observed on soticlestat treatment.

Mahnaz Asgharnejad, PharmD

New 2-year data from the open-label extension (OLE) of the phase 2 ENDYMION 1 study (NCT03635973) showed that treatment with soticlestat (Takeda Pharmaceutical), an antiseizure medication, was associated with high rates of caregiver-reported satisfaction. Across non-seizure symptoms/impacts faced by patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS), the highest levels of caregiver-reported improvement were in verbal and non-verbal communication.¹

ENDYMION 1 is a multi-site, open-label, extension study assessing the long-term safety and tolerability of soticlestat, also known as TAK-935, in patients with developmental and epileptic encephalopathies like LGS and DS. In the trial, patients receive soticlestat twice a day, with site visits every 2-6 months throughout the study. The new analysis, presented at the 2023 American Epilepsy Society (AES) annual meeting, held December 1-5, in Orlando, Florida, evaluated caregiver experience of treatment satisfaction and impacts on non-seizure symptoms with long-term use of soticlestat.

Led by Mahnaz Asgharnejad, PharmD, vice president, Global Program Leader, Takeda Pharmaceuticals, 62 caregivers of patients with LGS or DS on the drug completed at least 1 questionnaire item of the Experience Questionnaire at 1 study visit. Patient and caregiver experience was evaluated every ~26 weeks, with the analysis focusing on responses after ~2 years of treatment.

At week 104, 44 caregivers responded to the questionnaire, with a majority reporting overall satisfaction with soticlestat (75.0%) and its administration (72.7%). More specifically, 42.4% (14 of 33) of those satisfied with treatment were reportedly extremely or very satisfied while 59.4% (19 of 32) of those satisfied with administration were considered extremely or very satisfied. Notably, one-fifth (20.5%) of caregivers reported improvements in alertness, and most reported no change or improvement across symptoms/impacts.

Based on questionnaire responses, caregivers noted improvements in verbal communication (46.9%), non-verbal communication (45.5%), and engagement (39.5%) at 104 weeks. Most caregivers who reported improvement in these 3 items rated the change as meaningful (verbal: 14 of 15; non-verbal: 17 of 20; engagement: 11 of 17). The study also allowed caregivers the option to include free-text responses. Using these responses, the most frequently mentioned positive impacts on day-to-day quality of life were on communication (17 mentions by 12 caregivers), and interaction and engagement (12 mentions by 8 caregivers).

ENDYMION is an open-label extension to ELEKTRA, a previously conducted phase 2 placebo-controlled study assessing 300 mg or less of twice daily, weight-adjusted soticlestat in children with DS and LGS. Published in Epilepsia in 2022, the trial enrolled 141 participants, 126 (86%) of which completed the study. ELEKTRA achieved its primary end point: the combined soticlestat-treated population demonstatrated a placebo-adjusted media reduction in seizure frequency of 30.21% during the maintenance period (n = 139; P = .0008).

Similar reductions were observed over the full 20-week treatment period, with soticlestat-treated patients demonstrating a placebo-adjusted median reduction in seizure frequency of 25.06% (95% CI, –42.48% to –10.69%; P = .0024). At the last study visit, responses on Clinical Global Impression-Clinician assessment indicated marked improvement in more patients on soticlestat than those on placebo (DS: 26.9% vs 8.0%; LGS: 27.9% vs 11.1%). These results were reflected by caregivers, with Care GI-C responses that indicated improvement in more patients on active treatment (DS: 57.7% vs 32.0%; LGS: 51.2% vs 28.9%).

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REFERENCES
1. Asgharnejad M, Andrews JS, Mitra P, et al. Caregiver-reported overall treatment experience and change in non-seizure symptoms/impacts in the ENDYMION1 study of soticlestat (TAK-935) in individuals with Dravet or Lennox-Gastaut syndrome. Presented at: 2023 AES annual meeting; December 1-5; Orlando, FL. Abstract 1.282