Authors :
Presenting Author: Dylan Huynh, BS – Mid Atlantic Epilepsy and Sleep Center
Ivana Tyrlikova, MD – Mid Atlantic Epilepsy and Sleep Center; Salman Hashmi, MD – Mid Atlantic Epilepsy and Sleep Center; Keren Lefranc, BS – Mid Atlantic Epilepsy and Sleep Center; Abigail Heath, BS – Mid Atlantic Epilepsy and Sleep Center; Sriman Maddineni, BS – Mid Atlantic Epilepsy and Sleep Center; Alexander Giermek, BS – Mid Atlantic Epilepsy and Sleep Center; Pavel Klein, MD – Mid Atlantic Epilepsy and Sleep Center
Rationale:
Long term efficacy and tolerability of cenobamate (CNB) in clinical practice were assessed.
Methods:
This is a prospective open label study of all epilepsy patients treated at a single center with CNB since 2011. The analysis includes both patients initially enrolled in the pivotal CNB trials of patients with drug-resistant (DRE) focal epilepsy (FE) (NCT01397968 [2011-2013), NCT01866111 [2013-2015], and NCT02535091 [enrollment 11/3/2015-2/8/2018], and patients treated commercially since 2020.
≥50%-, 75%-, 90%- and 100% responder rates (RR, seizure reduction from baseline) were assessed for the whole treatment period and for the maintenance treatment period, defined as treatment for ≥1 month after the last maximum CNB dose adjustment at ≥50 mg/day until analysis date or treatment discontinuation. Treatment-emergent adverse events (TEAEs) were assessed. Patients who stopped CNB at
£25 mg/day dose or were lost to follow up before reaching maximum tolerated dose were counted as non-responders.Results:
Two hundred twenty one patients were treated. Current analysis includes only patients treated for
≥6 months and patients who stopped CNB at
£6 months due to TEAEs, n=177, 51.4% female, age range 17-75 years. 171/177 (96.6%) patients had focal-onset seizures (FOS), 6/177 (3.4%) generalized-onset seizures. 15/177 (8.5%) had DEE. 66 %(113/171) of FE patients had TLE, 14% FLE, 6% other foci,14% had no EEG focus. Patients had mean 5.7 (range 1-19) prior antiseizure medications (ASMs) and 2.3 (range, 1-5) concomitant ASMs at index. Median epilepsy duration was 23 years. Median maintenance dose was 250 mg/day (range 12.5-450, Q1–Q3, 200–350). Median CNB treatment duration was 16.5 months (range, 0.43-114, Q1–Q3, 7.3-32.8 months;). 14.7% (26/177) patients were treated for ≥5 years, 18.6% for ≥3-, and 37.3% for ≥2 years. 49/177 (27.7%) patients stopped CNB, including 9/177 (5.1%) at £25 50 mg/day dose and 9.6% at 50-200 mg/day. 22/177 (12.4%) patients did so because of TEAEs (including 8/177 (4.5%) with final dose £25 mg/d), 23 (13%) because of lack of efficacy and 4 for other reasons. 11/177 (6.2%) were lost to follow up. 100%, ≥90%, ≥75%, ≥50% RRs were 17.0% (30/177), 36.2%, 47.5% and 62.7% for the whole treatment period and 37.3% (66/177), 49.2%, 59.3% and 71.8% for the maintenance period. Among 100%- and ≥90% seizure reduction responders, 38/64 (59.38%) reached the response at £25 mg/day and 6/64 (9.38%) at 50 mg/day. 28/105 (26.7%) patients with 100%-, 90%- and 75% seizure frequency reduction discontinued 1, 6/105 (5.7%) 2, and 1/105 3 concomitant ASMs without losing seizure response.
Main TEAEs were somnolence (56.5%), fatigue (28.3%), dizziness (23.7%), ataxia (22.0%), headache (13.0%), diplopia (9.6%), dysarthria (7.3%), loss of appetite (7.3%), nausea (6.8%) and falls (5.1%). Main TEAEs leading to CNB discontinuation were somnolence (5.1%), ataxia (2.8%), rash (1.7%), dizziness (1.7%) and nausea (1.1%). No DRESS cases occurred.
Conclusions:
Our findings include longest CNB treatment follow up to-date. CNB appears highly effective (100% and
³90% seizure reduction) in a substantial proportion of patients
Funding:
None