Adding cannabidiol (CBD) to antiepileptic drug (AED) therapy
significantly reduces the frequency of drop seizures in patients with
Lennox-Gastaut syndrome (LGS), results of a phase 3 placebo-controlled study
have shown.
Although the add-on therapy resulted in more adverse events
than placebo, it was generally well tolerated, researchers report.
The new data are "exciting" because they represent
another possible step toward US Food and Drug Administration (FDA) approval of
this agent and give "new hope" to patients with LGS, lead researcher,
Anup Patel, MD, associate professor of neurology and pediatrics, Nationwide
Children's Hospital and The Ohio State University Medical Center, Columbus,
told Medscape Medical News. "If approved, we will have another option to use in a
disease state that tends to be very treatment-resistant," he said.
The study results were released April 18 and will be
presented in full at the American Academy of Neurology 2017 Annual Meeting
(AAN) in Boston, Massachusetts…
The multicenter study included 225 patients with LGS, with a
mean age of 16 years (30% were adults; the oldest was 55 years old). These
patients had experienced eight or more drop seizures during a 4-week baseline
period, with failure of at least one AED.
Their median monthly drop seizure frequency was 85. A median
of six AEDs had previously failed, and patients were currently taking a median
of three AEDs.
Researchers randomly assigned patients to receive CBD
(Epidiolex; GW Pharmaceuticals), 20 mg/kg/day; CBD, 10 mg/kg/day; or placebo.
After a 2-week titration period, patients continued on therapy for 12 weeks…
The primary efficacy endpoint was percentage change from
baseline in drop seizures, which tend to be the most prevalent type of seizures
in patients with LGS, according to Dr Patel.
"More importantly, they are the most disabling type of
seizures and have a greater risk of injury," he said.
Of the total, 9 patients in the 20-mg/kg CBD group and 2
each in the 10-mg/kg CBD and placebo groups withdrew from the study early.
The analysis found that compared with placebo (with a
percentage change of 17%), the reduction in drop seizure frequency was significantly
greater for CBD 20 mg/kg (42%; P = .0047) and CBD 10 mg/kg (37%; P = .0016).
Adverse events occurred in 94% of the 20-mg/kg CBD group,
84% of the 10-mg/kg CBD group, and 72% of the placebo group. Most of these were
mild or moderate. The two most common adverse events, occurring in greater than
10% of patients, were somnolence and decreased appetite.
Treatment-related serious adverse events were reported in 5
patients receiving CBD 20 mg/kg, 2 receiving CBD 10 mg/kg, and 0 receiving
placebo.
Overall, 13 patients had elevated aminotransferase levels,
which may indicate liver problems. But Dr Patel pointed out that 10 of these
patients were also taking the AED valproic acid, which may have contributed to
this elevation…
Dr Patel pointed out that those in the placebo group as well
as those taking the active agent had a high rate of adverse events.
"Obviously, the rate was higher in the treatment arms,
but it was very similar to the overall percentage of [adverse events] noted in
other trials of patients with LGS," he said. "This is a very sick
population of patients and they often have other problems."
He also stressed that the number of patients who dropped out
of the study was small.
Of the 212 completers, 99% entered the open-label extension
study.
Study results of the drug in LGS have been released before,
but what's new here, said Dr Patel, is that researchers have added results on
responder rates (a 50% or greater reduction in monthly drop seizures) and from
the Caregiver Global Impression of Change (CGI) questionnaire, which is a sort
of "marker for quality of life."
The drug outperformed placebo on both these outcomes, said
Dr Patel.
The responder rate was 15% in the placebo group vs 36% in the lower-dose CBD group (P = .0030)
and 40% in the higher-dose group (P = .0006).
As for the CGI, 66% of patients taking the lower dose and
57% taking the higher dose reported an improvement in overall condition
compared with 44% for placebo (P < .05 for both comparisons)…
Commenting on these findings for Medscape Medical News, Amy
Brooks-Kayal, MD, chief and Ponzio Family Chair in Pediatric Neurology,
University of Colorado, Denver, and former president of the American Epilepsy
Society (AES), pointed out that these results are similar to the seizure
reductions reported in several abstracts presented in December 2016 at the AES
meeting in Houston, Texas.
"These results suggest that CBD may be an effective
adjunctive therapy in treatment-resistant epilepsy, and can be effective in
reducing seizure frequency, but with a high rate of adverse effects and low
rate of seizure freedom," she said.
http://www.medscape.com/viewarticle/878883
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