Authors :
Presenting Author: Mahnaz Asgharnejad, PharmD – Takeda Pharmaceutical Company, Ltd
J Scott Andrews, PharmD – Takeda Pharmaceutical Company, Ltd; Pranab Mitra, PhD – Takeda Pharmaceutical Company, Ltd; Lara Sams, MSc – Clinical Outcomes Solutions; Jennifer Beaumont, MS – Clinical Outcomes Solutions; Shruti Dave, PhD – Clinical Outcomes Solutions; Samuel Hsiao, PhD – Takeda Pharmaceutical Company, Ltd; Naga Venkatesha Murthy, MD – Takeda Pharmaceutical Company, Ltd; Arturo Benitez, MD, MBA – Takeda Pharmaceutical Company, Ltd; Tara Symonds, PhD – Clinical Outcomes Solutions; Drishti Shah, PhD – Takeda Pharmaceutical Company, Ltd
Rationale:
Soticlestat (TAK-935) is a selective inhibitor of cholesterol 24-hydroxylase being investigated as potential therapy for Lennox-Gastaut (LGS) and Dravet (DS) syndromes. We evaluated caregiver experience of treatment satisfaction and impacts on non-seizure symptoms with long-term use of soticlestat in the ENDYMION 1 study.
Methods:
ENDYMION 1 (NCT03635073) is an ongoing, global, phase 2, open-label extension (OLE) study of twice-daily oral soticlestat including individuals ( ³ 2 y) with LGS or DS. Patient and caregiver experience is assessed every ~26 weeks. The Experience Questionnaire asks caregivers to rate experience with study medication over the prior four weeks and any observed changes in non-seizure symptoms/impacts from a caregiver perspective. Caregivers had the option to include free-text responses. This analysis focused on responses after ~2 years of treatment.
Results:
Sixty-two caregivers completed ³ one questionnaire item at ³one study visits. The study participants with LGS/DS had a mean (SD; range) age of 10.0 y (3.8; 3–18), 61.3% were male, 66.1% were White and 33.9% Asian, 62.9% had LGS and 37.1% had DS. Forty-four caregivers responded to the questionnaire at the Week 104 visit. At Week 104, the majority of caregivers reported overall satisfaction with soticlestat (75.0%) and its administration (72.7%; Table 1). Among those satisfied with treatment, 42.4% (14/33) reported being extremely or very satisfied. Among those satisfied with administration, 59.4% (19/32) reported being extremely or very satisfied. Across symptom/impact items, the highest percentages of caregivers reporting improvement were in verbal communication (46.9%), non-verbal communication (45.5%), and engagement (39.5%; overall at Week 104; Table 2). Most caregivers who reported improvement in these three items rated the change as meaningful (14/15 verbal; 17/20 non-verbal; 11/17 engagement); at least half of those reporting minimal improvement for these three items stated that level of change was meaningful to them. About a fifth of caregivers (20.5%) reported improvement in alertness; most reported either no change or improvement across symptoms/impacts. Consistent with these results, the most frequently mentioned positive impacts on day-to-day life from free text responses across all study visits were improved communication (17 mentions by n=12 caregivers), and interaction and engagement (12 mentions by n=8).
Conclusions:
After 2 years of soticlestat treatment in the ENDYMION 1 OLE study, most caregivers reported satisfaction with overall treatment and administration. Across non-seizure symptoms/impacts experienced by individuals with LGS or DS, the highest levels of caregiver-reported improvement were in verbal and non-verbal communication. The small sample size, potential for selection bias, and non-response bias due to only analyzing those who responded to the questionnaire at Week 104 may limit interpretation of the results.
Funding:
Takeda Pharmaceutical Company Ltd.