DROP SEIZURE REDUCTION
EPIDIOLEX® (cannabidiol) significantly reduced drop seizure frequency in patients living with LGS
A prespecified exploratory analysis evaluated the effect of EPIDIOLEX® (cannabidiol) on drop seizure reduction in the subgroup of patients receiving clobazam6
Adult patients: Reduction in drop seizure frequency with EPIDIOLEX® (cannabidiol)7
Reduction in monthly frequency of drop seizures
Among patients taking clobazam, those also taking EPIDIOLEX experienced a greater reduction in drop seizures than with placebo6
Prespecified exploratory subgroup analysis: Drop seizure reduction in adult patients
Reduction in monthly frequency of drop seizures among adult patients7
Note: 49% of patients in LGS clinical trials were taking concomitant clobazam. Subgroup analysis is exploratory and descriptive in nature.
Note: Adult data represents ~1/3 of the total trial population.1,2 Subgroup analysis is exploratory and descriptive in nature.
Results from the 14-week treatment period. Drop seizures were defined as atonic, tonic, or tonic-clonic seizures that led to or could have led to a fall or injury.1,2
Patients at baseline1,2:
- Had previously tried a median of 6 prior ASMs
- Currently uncontrolled with a median of 3 current ASMs
94% of patients were taking ≥2 ASMs at baseline and still experiencing a median of 74 and 85 drop seizures (Study 1 and Study 2, respectively) per 28 days.1,2
The most commonly used concomitant ASMs were:
49% clobazam |
39% valproate |
33% lamotrigine
Reductions in drop seizure frequency were reported as early as Day 6 in a post hoc analysis of the LGS clinical trials.3
Recommended daily dosage is 10 mg/kg/day (5 mg/kg twice daily), with a maximum maintenance dosage of 20 mg/kg/day (10 mg/kg twice daily).
Administration of the 20 mg/kg/day dosage resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10 mg/kg/day, but with an increase in adverse reactions. Patients with moderate to severe hepatic impairment require a dose adjustment.
Important considerations for your patients taking EPIDIOLEX and clobazam:
- EPIDIOLEX can cause somnolence and sedation that generally occurs early in treatment and may diminish with continued treatment. These effects were more common in patients on concomitant clobazam
- Pneumonia was observed more frequently with concomitant use of EPIDIOLEX and clobazam
- Elevated ammonia levels have been reported in some EPIDIOLEX-treated patients who also had transaminase elevations. Most cases reported concomitant use of valproate, clobazam, or both
- Consider a reduction of dosage or discontinuation of clobazam if known clobazam adverse reactions occur
- Other CNS depressants, including alcohol, could potentiate the somnolence and sedation effect of EPIDIOLEX
- Monitor for somnolence and sedation and advise patients not to drive or operate machinery until they have gained sufficient experience on EPIDIOLEX
- Rapid withdrawal of ASMs can lead to increased seizure frequency and status epilepticus
Results from the 14-week treatment period. Drop seizures were defined as atonic, tonic, or tonic-clonic seizures that led to or could have led to a fall or injury.1,2
TOTAL SEIZURE REDUCTION
EPIDIOLEX® (cannabidiol) significantly reduced total seizures in patients living with LGS
A post hoc exploratory analysis evaluated the effect of EPIDIOLEX® (cannabidiol) on total seizure reduction in the subgroup of patients receiving clobazam6
Reduction in monthly frequency of total seizures
Among patients taking clobazam, those also taking EPIDIOLEX experienced a greater reduction in total seizures than with placebo6
Note: 49% of patients in LGS clinical trials were taking concomitant clobazam. Subgroup analysis is exploratory and descriptive in nature.
Results from the 14-week treatment period. Total seizures included drop and non-drop seizures.1,2
The baseline frequency of total seizures (median) in Study 1 was 177 in the placebo group and 145 in the EPIDIOLEX 20 mg/kg/day group.1
In Study 2, the baseline frequency of total seizures (median) was 181 in the placebo group, 165 in the EPIDIOLEX 10 mg/kg/day group, and 174 in the EPIDIOLEX 20 mg/kg/day group.2
Important considerations for your patients taking EPIDIOLEX and clobazam:
- EPIDIOLEX can cause somnolence and sedation that generally occurs early in treatment and may diminish with continued treatment. These effects were more common in patients on concomitant clobazam
- Pneumonia was observed more frequently with concomitant use of EPIDIOLEX and clobazam
- Elevated ammonia levels have been reported in some EPIDIOLEX-treated patients who also had transaminase elevations. Most cases reported concomitant use of valproate, clobazam, or both
- Consider a reduction of dosage or discontinuation of clobazam if known clobazam adverse reactions occur
- Other CNS depressants, including alcohol, could potentiate the somnolence and sedation effect of EPIDIOLEX
- Monitor for somnolence and sedation and advise patients not to drive or operate machinery until they have gained sufficient experience on EPIDIOLEX
- Rapid withdrawal of ASMs can lead to increased seizure frequency and status epilepticus
RESPONDER RATES
EPIDIOLEX® (cannabidiol) cut seizure frequency by ≥50% and ≥75% in more patients than placebo in the LGS trials
A prespecified exploratory analysis evaluated the effect of EPIDIOLEX® (cannabidiol) on seizure frequency in the subgroup of patients receiving clobazam6
Responder rates in adult patients taking EPIDIOLEX® (cannabidiol)7
Responder rates (≥50% and ≥75% reductions in drop seizures from baseline)1,2
Among patients taking clobazam, those also taking EPIDIOLEX experienced a greater reduction in seizure frequency than with placebo6
Prespecified exploratory subgroup analysis: ≥50% seizure reduction in adult patients7
≥50% reduction in drop frequency from baseline among adult patients7
Note: 49% of patients in LGS clinical trials were taking concomitant clobazam. Subgroup analysis is exploratory and descriptive in nature.
Note: Adult data represents ~1/3 of the total trial population. Subgroup analysis is exploratory and descriptive in nature.
≥50% reduction in drop frequency from baseline among adult patients7
STUDY 1
STUDY 2
Note: 49% of patients in LGS clinical trials were taking concomitant clobazam. Subgroup analysis is exploratory and descriptive in nature.
Note: Adult data represents ~1/3 of the total trial population.1,2 Subgroup analysis is exploratory and descriptive in nature.
Results from the 14-week treatment period.1,2
More patients achieved freedom from drop seizures with EPIDIOLEX than with placebo.
4%
EPIDIOLEX
10 mg/kg/day
5%
EPIDIOLEX
20 mg/kg/day
0.6%
PLACEBO
Important considerations for your patients taking EPIDIOLEX and clobazam:
- EPIDIOLEX can cause somnolence and sedation that generally occurs early in treatment and may diminish with continued treatment. These effects were more common in patients on concomitant clobazam
- Pneumonia was observed more frequently with concomitant use of EPIDIOLEX and clobazam
- Elevated ammonia levels have been reported in some EPIDIOLEX-treated patients who also had transaminase elevations. Most cases reported concomitant use of valproate, clobazam, or both
- Consider a reduction of dosage or discontinuation of clobazam if known clobazam adverse reactions occur
- Other CNS depressants, including alcohol, could potentiate the somnolence and sedation effect of EPIDIOLEX
- Monitor for somnolence and sedation and advise patients not to drive or operate machinery until they have gained sufficient experience on EPIDIOLEX
- Rapid withdrawal of ASMs can lead to increased seizure frequency and status epilepticus
of patients in the LGS studies taking concomitant clobazam with either dose of EPIDIOLEX reported a dose reduction of clobazam during the trial.7
Results from the 14-week treatment period.1,2
3-YEAR OPEN-LABEL EXTENSION
3-year sustained reduction of drop seizures8
Open-label extension: Reduction in monthly frequency of drop seizures8
WEEKS
Decreasing n-values reflect a combination of discontinuations and rolling entry into the open-label extension trial.9
- Retention rates at 1, 2, and 3 years were 81%, 69%, and 65%, respectively9
- 30% (n=37) of withdrawals were due to adverse reactions8
- LOCF sensitivity analyses showed no impact of withdrawn patients on change in seizure frequency9
Reductions in total seizure frequency were also maintained with long-term treatment.8
Adverse events:
- The long-term safety profile of EPIDIOLEX® (cannabidiol)in this open-label extension trial was generally similar to that observed in the EPIDIOLEX clinical development program8
- Eleven deaths were reported in patients with LGS; none were deemed to be treatment-related by the investigator8
- In the open-label extension trial, titration to doses over 20 mg/kg/day was permitted. At higher doses, an increase in adverse reactions was observed8
of patients with LGS who completed controlled clinical trials chose to continue into the open-label extension.8
LEARN MORE
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