This additional application, supported by data from the GWPCARE6 trial, seeks to expand the indication of cannabidiol to include seizures associated with tuberous sclerosis complex.
GW Pharmaceuticals announced that it has submitted a supplemental new drug application (sNDA) for its cannabidiol (CBD; Epidiolex) oral solution to expand its indication to include seizures associated with tuberous sclerosis complex (TSC).1
The therapy was originally approved for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome for patients age 2 and older in 2018. It was rescheduled by the DEA to Schedule V in September of that year.
"The submission of this sNDA for Epidiolex is an important step towards the prospect of offering a new treatment option for those patients with TSC who battle difficult-to-treat seizures," Justin Gover, CEO of GW Pharmaceuticals, said in a statement. "Having already obtained approval for Epdiolex in the treatment of seizures associated with Lennox-Gastaut Syndrome and Dravet Syndrome, this submission is based on positive phase 3 data showing that Epidiolex reduced TSC-associated seizures, which include both focal and generalized seizures types.”
“We look forward to working with the FDA toward an expected approval later this year," he added.
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This new application is supported by data from GWPCARE6, a phase 3 safety and efficacy assessment, the findings of which were presented at the American Epilepsy Society’s 2019 Annual Meeting in Baltimore, Maryland. The data from the trial were presented by Elizabeth Thiele, MD, PhD, director of pediatric epilepsy and the Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital, and professor of neurology at Harvard Medical School.2
All told, those treated with CBD experienced reductions in TSC-associated seizure frequency of 49% with the 25 mg/kg dose and 48% for the 50 mg/kg dose, nearly double that of the placebo group, which experienced reductions of 27% (25 mg: P = .0009; 50 mg: P = .0018).
Importantly, the safety profile observed was consistent with findings from previous studies, with no new safety risks identified.
“Our findings suggest this formulation of purified CBD offers patients with TSC a new treatment option for their very difficult-to-manage seizures,” Thiele said in a statement at the time.3 “We also assessed 2 different daily doses and found the lower dose of 25 mg/kg of weight provides the same benefit with fewer side effects compared to a dose of 50 mg/kg and will likely be the recommended dose.”
GWPCARE6 included 224 patients-75 randomly assigned to the 25 mg group, 73 to the 25 mg group, and 76 to placebo. Overall, 201 patients completed the study. The median age was 11 years, with a median baseline monthly TSC-associated seizure frequency of 56 (interquartile range [IQR], 21–101) for the 25 mg group, 61 (IQR, 36–117) for the 50 mg group, and 54 (IQR, 26–102) for placebo. Prior to enrollment, patients had tried and discontinued a median of 4 antiepileptic drugs and were currently taking a mean of 3. The most common concomitant drugs were valproate (45%), vigabatrin (33%), levetiracetam (29%), and clobazam (27%).
Those who took CBD were more likely to experience a ≥50% reduction in seizures, observed in 36% of the 25 mg group (P = .0692) and 40% of the 50 mg group (P = .0245) compared to 22% for placebo. Caregivers reported an overall improvement in 69% of those taking 25 mg of CBD, 62% of those taking 50 mg, and 40% of those who received placebo.
The CBD groups also saw significantly greater reduction in total seizure frequency compared to placebo: 48% for 25 mg (P = .0013), 48% for 50 mg (P = .0018), and 27% for placebo. Improvement in overall condition on the Clinical Global Impression of Change (CGIC) was reported by 69% (odds ratio [OR], 2.25; P = .0074) of patients/caregivers for the 25 mg group and 62% (OR, 1.77; P = .0580) for 50 mg, compared to 40% for placebo.
1. GW Pharmaceuticals and Greenwich Biosciences Submit Supplemental New Drug Application to U.S. FDA for Epidiolex® (cannabidiol) for the Treatment of Tuberous Sclerosis Complex [press release]. London, UK, and Carlsbad, CA: GW Pharmaceuticals; Published February 3, 2020. biospace.com/article/releases/gw-pharmaceuticals-and-greenwich-biosciences-submit-supplemental-new-drug-application-to-u-s-fda-for-epidiolex-cannabidiol-for-the-treatment-of-tuberous-sclerosis-complex. Accessed February 3, 2020.
2. Thiele E, Wong M. Cannabidiol (CBD) treatment in patients with seizures associated with tuberous sclerosis complex: a randomized, double-blind, placebo-controlled phase 3 trial (GWPCARE6). Presented at: AES 2019; December 7–10; Baltimore, Maryland. Abstract 1.293.
3. Trial Shows CBD Helpful for Tuberous Sclerosis Complex-Related Seizures, May Expand Treatment Options for Challenging Form of Epilepsy [press release]. Baltimore, MD: American Epilepsy Soceity; Published December 7, 2019. Accessed February 3, 2020.