Epidyolex Safely Helps Prevent Seizures, Real-world Study Reports
50% drop in monthly seizures seen in Dravet patients in Spain on CBD treatment
The efficacy and safety of Epidiolex, an oral cannabidiol, in children and adults with Dravet syndrome and Lennox-Gastaut syndrome (LGS) were supported in a real-world setting, with benefits similar to those seen in previous clinical trials and expanded access programs (EAPs), a Spanish EAP study reported.
EAPs are designed to make promising therapies available to eligible patients in the real-world setting before their regulatory approval.
The study, “Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in pediatric and adult patients with epilepsy,” was published in the journal Epilepsy & Behavior.
Epidiolex (Epidyolex in EU) is an oral solution of highly purified CBD
Cannabinoids are a class of pharmacologically active compounds found in the cannabis plant, and include cannabidiol (CBD), cannabis’ main non-psychoactive component. Increasing evidence supports CBD’s therapeutic properties, including an ability to reduce seizure frequency in people with epilepsy.
Epidiolex, an oral solution of highly purified CBD, is approved in the U.S. and elsewhere for preventing seizures associated with Dravet and LGS in young children and adults.
In Europe, the therapy is sold as Epidyolex and approved in conjunction with the anti-seizure medication clobazam (brand names, Onfi and Sympazan) for young children and adults.
These approvals were supported by positive safety and efficacy data from several clinical trials, but “further insights are required on the most suitable combination, dosage, and titration for CBD use,” the researchers wrote.
Researchers at institutes across Spain retrospectively analyzed data from 102 Dravet and LGS patients (63 males and 39 females) who were given Epidyolex at 14 hospitals as part of a Spanish EAP.
All patients, with a mean age of 15.9 (58.4% younger than 15 years old), had at least six months of follow-up data. Sixty (58.8%) had LGS, 12 (11.8%) had Dravet syndrome, and 30 (29.4%) had other forms of epilepsy.
All were highly resistant to anti-seizure medications, having failed to respond to a mean of 7.5 of these treatments — the most common being Keppra (levetiracetam; 59.4% of these patients).
The study’s main goals were to assess the therapy’s safety and changes in seizure frequency, as well as the median relative seizure reduction between the study’s start (baseline) and a final visit. Secondary effectiveness goals included retention rate, reductions in seizure severity and in the number of status epilepticus episodes, healthcare utilization, and quality of life.
Status epilepticus, a common phenomenon in those with Dravet syndrome, describes epileptic episodes characterized by either a single seizure lasting longer than five minutes, or many seizures occurring close together without the patient recovering between them.
At baseline, participants were taking a mean of 3.4 anti-seizure medications, of which valproate was the most common (63.4% of patients), followed by clobazam (52.5%). Rescue medications, such as Valium (diazepam) and Versed (midazolam), were prescribed to most patients (68.2 %).
Non-pharmacological approaches being used included vagus nerve stimulation (25.5%) and ketogenic diet (27.5%).
Participants received distinct doses of Epidyolex for a mean of 10.3 months. At the last follow-up visit, the median dose was 10.2 mg/kg/day (430 mg/day). While pediatric patients (those under age 15) generally received higher mean doses than adult patients, these differences did not reach statistical significance.
50% drop in monthly convulsive seizures with treatment in Dravet patients
At baseline, patients experienced a median of 33 seizures and 15 most disabling seizures per month. After treatment, the median number of monthly seizures fell by 47.6% among all participants.
At study’s start, those with Dravet syndrome experienced 3.5 convulsive seizures per month, and these were reduced by 50% after treatment.
With six months of treatment, 44.9% of patients had at least a 50% reduction in the total number of seizures (called response rate); at their last visit this rate dropped to 36.4%. The response rate for most disabling seizures was 47.9% after six months and 38.5% at the patients’ last visit.
More than a quarter of these people reported no change in total seizure frequency (27.3%) and in disabling seizure frequency (28.6%), while these rates increased in less than 18% of the patients.
“Considering most disabling seizures, the outcomes in our study were also similar to those from an EAP conducted in 25 US centers,” the researchers wrote.
In an exploratory analysis, the researchers observed a better response in patients given Epidyolex and clobazam compared with those given Epidyolex alone. These included a higher percentage of responders for both total and disabling seizures. However, the researchers noted that this was only seen in up to three months of treatment.
No significant differences also were seen in the proportion of seizure-free patients or the proportion of responding patients when comparing pediatric and non-pediatric patients.
Response rates were always numerically higher for Dravet patients relative to those with LGS, but these differences only reached statistical significance up to three months of treatment (72.7% vs. 28.3%).
No significant differences were observed between these groups in terms of response for most disabling seizures.
After 12 months, seizure severity, assessed by the Caregiver’s Global Impression, eased in 61.1% of patients and remained unchanged in 31.5%.
“These outcomes are similar to those described in other EAPs for CBD,” the team added.
A greater number of patients experienced status epilepticus before treatment compared with the last six months of treatment (14 vs. two patients), but these differences carried no statistical significance.
“Larger studies are required to confirm the impact of CBD treatment on status epilepticus prevention,” the researchers wrote.
Quality of life was assessed using The Quality of Life of the Patient with Epilepsy (CAVE) scale, where higher scores indicate improvements. The CAVE score increased from a mean of 17.9 at baseline to 21.7 at last visit, reflecting a 21.2% improvement.
In agreement with these findings, researchers saw a trend toward reduced healthcare resource use after Epidyolex treatment.
A third of patients (33%) discontinued treatment during the study. Reasons included lack of effectiveness alone (6.9%), adverse events alone (7.8%), both (17.6%), and other reasons (1%).
A total of 66.7% patients experienced at least one adverse event, with the most common including somnolence (34.3%) and diarrhea (12.7%) — similar to that reported in clinical trials. Adverse events were considered mild in 27.5% of cases, moderate in 24.5%, and severe in 14.7%.
A greater proportion of Dravet patients experienced diarrhea (25% vs. 11.7%) and decreased appetite (16.7% vs. 3.3%) than those with LGS.
Overall, “CBD demonstrated promising effectiveness and tolerability in patients with” Dravet, LGS, and other forms of epilepsy “in a real-world setting,” the researchers wrote.
“The results of this study are broadly in alignment with those of other EAPs and randomized controlled trials. Further series are needed to provide a full picture of the use of CBD in clinical practice,” they concluded.
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