Abstracts

Rationale: The Idaho State Epidiolex EAP was established to provide access of CBD to children age 1 to 18 years with a confirmed diagnosis of medically intractable syndromic epilepsy who were not otherwise eligible for any ongoing clinical trials. Our program is designed primarily to assess safety and tolerability of adjunctive CBD in this patient population. We reported preliminary observations from our first cohort of 25 patients at AES in 2016. We now report subsequent observations from cohort 1 as well as from a second cohort of an additional 15 patients.  Methods: Enrollment in our program required at least 4 previously failed and appropriately selected anti-epileptic drug (AED) trials, including at least 1 combination therapy, without adequate seizure control. VNS, RNS, and ketogenic diet were considered therapeutic equivalents. All patients entered study on 1-4 background AEDs. Most patients are being referred by independent pediatric neurologists unaffiliated with our center, and were then evaluated at our center for inclusion. Visits are weekly during titration and quarterly once on stable dosing. Subjective seizure assessments are tracked in seizure diaries maintained by caregivers and tallied at each visit. Treatment emergent adverse events (AEs) also are tracked by caregivers and are collected at each visit. Background medication adjustments are deferred to the referring providers unless any AEs are deemed to mandate dose adjustment. Initial CBD oral solution (100 mg/mL) dose of 5 mg/kg/day was given orally in 2 divided doses and titrated by 5 mg/kg/day no more frequently than every 7 days, as tolerated, up to maximum dose of 25 mg/kg/day.  Results: One patient in cohort 1failed screening due to inability to tolerate blood draws, but was re-screened successfully in cohort 2. Thus a total of 39 patients entered the program. The 24 patients in the cohort 1 have been in program for at least a year. None have exited. The 15 patients entered into cohort 2 have been in the program for ≤6 months. One patient exited due to family relocation out of state. Of 39 patients, 25 had background AED regimen that included clobazam and 11 of those were also on valproate. One patient had valproate without clobazam, while 14 had clobazam without valproate.Subjective seizure improvement was reported by 20 of 24 patients in cohort 1 (83%) and by 11 of 14 patients in cohort 2 (79%). AEs have been reported by 17 of 39 patients (44%). Lethargy and sedation were the most common AEs, reported in 12 (30.0%), 10 of whom were on clobazam and valproate in combination when CBD was added. Improved tolerability was reported with decreases of background AED doses in these 10. Sedation has persisted in 2 to date. Aggression has been reported in 4 (10.0%). Diarrhea has been reported in 4 (10.0%). Dose adjustment of background AEDs improved AEs in 13 of 17 patients to date. Clobazam dose was reduced in 10 and valproate dose was reduced in 5. No reduction of CBD dose has been required.  Conclusions: This is an open-label, expanded access program actively following 38 patients in two cohorts. Subjective reports of improvement in seizures must be interpreted cautiously but some patients appear to have derived benefit from treatment. CBD appears to be well tolerated. Lethargy and sedation are the most commonly encountered adverse events, particularly in patients on clobazam and valproate in their background AED regimen. Most AEs have resolved with decreases of background AED dose. Funding: No funding was received in support of this abstract. The Idaho Epidiolex EAP was created by Executive Order of our Governor and is overseen and funded by the Idaho Department of Health and Welfare. Epidiolex is provided free of charge by GW Research Ltd UK, operating in the US through its subsidiary, Greenwich Biosciences, Inc.