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PHILADELPHIA – There's still only open-label evidence for the efficacy of cannabidiol (Epidiolex) in epilepsy, but results from randomized controlled trials are expected soon, researchers reported here.

In an updated analysis of data from the largest open-label program, patients had a mean reduction in seizure frequency of 45% over 3 months, , of NYU Langone Medical Center, reported during a press briefing at the here.

A year-long open-label study of 25 patients found that 40% of patients had at least a 50% reduction in seizures over 1 year of taking cannabidiol, but a large proportion had dropped out because the drug didn't work, according to , formerly of the University of California San Francisco and now at the University of Louisville in Kentucky.

"This kind of response rate in such a treatment-resistant group was promising, but without a double-blind study, we are blind to the real outcome," Devinsky said during the briefing. "This adds more fuel to the fire that this drug is definitely likely to be effective for some people. How it holds up against placebo we'll have to see."

Drugmaker GW Pharmaceuticals is currently conducting four randomized controlled trials of its marijuana-derived drug candidate in epilepsy: two in Dravet Syndrome and two in Lennox-Gastaut Syndrome (LGS).

Devinsky said one of the trials in Dravet Syndrome is complete and should be reporting results by the end of February.

In the meantime, he delivered an update of the open-label program he's leading, which now has 261 patients enrolled. Their mean age was 12 years, they were taking an average of 3 other anti-epileptic drugs, and 17% had Dravet Syndrome and 15% had LGS.

Patients were uptitrated to a maximum daily dose of 25 mg/kg or whatever was tolerated, and the study ran for 12 weeks.

Devinsky and colleagues found a mean reduction in seizure frequency of 45% over those 3 months, which was even higher, at 63%, for those with Dravet Syndrome.

Those with LGS had a mean reduction in atonic seizures of 71% from baseline, Devinsky said.

Overall, about half (47%) had at least a 50% reduction in seizures, and 9% were seizure-free at 3 months – a figure that was, again, higher for Dravet patients at 13%.

Devinsky noted that clobazam co-therapy was associated with higher rate of treatment response, which may reflect elevations in the desmethyl clobazam metabolite.

Common adverse events included somnolence (23%), diarrhea (23%), fatigue (17%), decreased appetite (17%), convulsions (17%), and vomiting (10%).

A small proportion (4%) stopped the drug because of side effects, and 12% withdrew for lack of effectiveness.

About a third of patients (34%) experienced serious adverse effects, and there were seven deaths. All of the fatalities were determined not to be related to the study drug, and the number was not considered to be surprising because this population has high rates of sudden unexplained death in epilepsy (SUDEP) and status epilepticus, Devinsky said.

In a smaller study of 25 patients – average age 9, taking two other anti-epileptic drugs -- treated at the University of California San Francisco with cannabidiol and tracked for 1 year, Oldham and colleagues found 32% responded to cannabidiol at 3 months and 3 patients were seizure-free (two of these were Dravet patients).

By 1 year, 40% of patients had at least a 50% reduction in seizures – but 12 of the 25 patients had stopped the drug for lack of efficacy, and one had a marked increase in seizure frequency due to cannabidiol, Oldham said.

"This is a significantly drug-resistant population, so the fact that we found a third to 45% of patients with a greater than 50% reduction is quite remarkable," Oldham said. "This definitely supports doing randomized controlled trials to see if the benefit plays out."

The four pivotal trials are being conducted at 50 epilepsy centers in the U.S., totaling more than 500 patients with Dravet Syndrome or LGS.