Topline results of a new phase 3 trial show that cannabidiol (CBD; Epidiolex, GW Pharmaceuticals) outperformed placebo in controlling seizures in patients with Lennox-Gastaut syndrome (LGS), a rare and severe form of childhood-onset epilepsy, the company has announced.
It was the second randomized, double-blind, placebo controlled phase 3 trial of the investigational medicine in this patient population released this year.
"The positive outcome in this second trial of cannabidiol in patients with Lennox-Gastaut syndrome demonstrates the effectiveness of this product in this particularly difficult to treat, childhood-onset epilepsy," the trial's principal investigator, Orrin Devinsky, MD, New York University Langone Medical Center's Comprehensive Epilepsy Center, said in statement.
In June, the company announced positive results in the first pivotal phase 3 trial of cannabidiol for treating seizures associated with LGS. Just a few months earlier — in March 2016 — it announced positive results in the treatment of seizures associated with Dravet syndrome, another rare childhood condition.
Cannabidiol has Orphan Drug Designation status from the US Food and Drug Administration (FDA) for the treatment of LGS, Dravet syndrome, tuberous sclerosis complex, and infantile spasms.
GW expects to submit a New Drug Application (NDA) to the FDA in the first half of 2017.
Clinically Meaningful
"The data from the Epidiolex Dravet and LGS studies offers the prospect of an FDA-approved CBD medicine that shows both clinically meaningful seizure reduction and a consistent safety and tolerability profile," said Dr Devinsky. "I believe Epidiolex has the potential to become an important new option within the field of treatment-resistant epilepsy."
This most recent trial randomly assigned 225 patients with drug-resistant LGS into three groups: cannabidiol 20 mg/kg per day (n = 76), cannabidiol 10 mg/kg per day (n = 73), or placebo (n = 76). Patients were taking about three antiepileptic drugs, having previously tried and discontinued an average of seven other antiepileptic drugs.
The average age of trial participants was 16 years (30% were 18 years or older). The median drop-seizure frequency during the 4-week baseline period was 85.
Drop seizures were defined as atonic, tonic, or tonic-clonic seizures involving the entire body, trunk, or head that led or could have led to a fall, an injury, slumping in a chair, or the patient's head hitting a surface.
The trial included a 2-week dose escalation period followed by 12 weeks of maintenance. It compared this 14-week period to the 4-week baseline period before randomization.
The trial found that patients taking cannabidiol 20 mg/kg per day achieved a median reduction in monthly drop seizures of 42% compared with 17% in patients taking placebo (P = .0047). Those taking cannabidiol 10 mg/kg per day achieved a median reduction in monthly drop seizures of 37% compared with 17% in patients taking placebo (P = .0016).
A series of sensitivity analyses confirmed the robustness of these results. In both groups, the difference between cannabidiol and placebo emerged during the first month of treatment and was sustained during the entire treatment period.
This latest trial shows that cannabidiol likely has an effective dose range, allowing for dose flexibility to address individual patient needs, Justin Gover, GW's chief executive officer, said in the statement.
Cannabidiol was generally well tolerated, with the pattern of adverse events (AEs) being consistent with that reported in the previous two phase 3 studies. One patient receiving the lower dose discontinued treatment because of an AE compared with six patients receiving the higher dose and one patient receiving placebo.
Most AEs were mild or moderate. Among the most common in both groups (occurring in greater than 10%) were somnolence, decreased appetite, upper respiratory tract infection, and diarrhea. Status epilepticus was also a common AE in the lower-dose group, but none of these cases was deemed treatment related.
Thirteen patients in both treatment groups experienced a serious AE. Two of these in the lower-dose group and five in the higher-dose group were deemed treatment related. Eight patients receiving placebo had a serious AE, none of which were deemed treatment related. No patients died.
Of the patients who completed this trial, 99% have opted to continue into an open-label extension trial, according to the press release.
The new announcement was met with enthusiasm from various groups representing seizure conditions. "Today brings great news for the Lennox-Gastaut Syndrome community," said Christina SanInocencio, executive director of the Lennox-Gastaut Syndrome Foundation, in the press release.
"The announcement of a second set of positive results with cannabidiol is exciting as they offer much needed hope for patients and their families living with this debilitating condition where new treatment options are desperately needed."
The Epilepsy Foundation is "thrilled" to learn about the preliminary results for an "innovative new therapy" for LGS, said Philip Gattone, president and chief executive officer of the Epilepsy Foundation, also quoted in the GW release. "LGS in so many cases is extremely difficult to treat, and is an incredible challenge for children and families."
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Cite this: More Positive Topline Results for Cannabidiol in LGS - Medscape - Sep 28, 2016.
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