A cannabidiol oral solution for use as adjunctive therapy of childhood seizures is the first plant-derived cannabis-based medicine to be approved by the European Medicines Agency (EMA).

The European Commission approved the marketing authorisation for Epidyolex, which contains highly purified, plant-derived cannabidiol (CBD), a cannabinoid lacking the “high” associated with cannabis, for use as adjunctive therapy of seizures associated with Lennox‑Gastaut syndrome (LGS) or Dravet syndrome, in conjunction with clobazam, for patients two years of age and older. The approval paves the way for the launch of the medicine across Europe.

“The approval of cannabidiol oral solution is an important milestone for patients and families whose lives are significantly impacted by these rare, complex and life-long forms of epilepsy,” said Isabella Brambilla, Chairman, Dravet Syndrome European Federation. “We are very happy that patients will now have access to a much-needed, new treatment option, and one routed through a rigorous clinical trials programme and licensed by the EMA.”

The approval of cannabidiol oral solution is based on results from four randomised, controlled Phase 3 trials. These studies incorporate data from more than 714 patients with either LGS or Dravet syndrome, two rare forms of epilepsy with high morbidity and mortality rates, which place a significant burden on families and caregivers. Many patients with LGS or Dravet syndrome have multiple seizures per day, which puts them at ongoing risk of falls and injury. Despite current anti-epileptic drug treatment, both of these severe forms of epilepsy remain highly treatment-resistant.

New treatment for most severe forms of childhood onset epilepsy

“LGS and Dravet syndrome are two of the most severe and difficult-to-treat forms of childhood-onset epilepsy, with few patients achieving adequate seizure control,” said Professor Elinor Ben-Menachem, University of Goteborg, Sahlgren Academy and Hospital in Sweden. “The EMA approval of  Epidyolex will bring hope to patients and families, with the potential to better control seizures and improve quality of life.”

When added to other anti-epileptic therapies, Epidyolex significantly reduced the frequency of seizures in patients with LGS and Dravet syndrome. The most common adverse reactions that occurred in patients treated with the medicine were somnolence, decreased appetite, diarrhoea, pyrexia, fatigue and vomiting. 

GW’s cannabidiol oral solution was approved by the US Food and Drug Administration (FDA) in June 2018 under the trade name Epidyolex for the treatment of seizures associated with LGS or Dravet syndrome in patients two years of age or older.

The EC decision is valid in all 28 countries of the European Union, alongside Norway, Iceland and Liechtenstein.

What is Dravet syndrome?

Dravet syndrome is a severe infantile-onset and highly treatment-resistant epileptic encephalopathy frequently associated with genetic mutations in the sodium channel gene SCN1A. Onset of Dravet syndrome occurs typically during the first year of life in previously healthy and developmentally normal infants. Initial seizures are often body temperature related, severe, and long-lasting.

Over time, patients with Dravet syndrome often develop multiple types of seizures, including tonic-clonic, myoclonic and atypical absences and are prone to bouts of prolonged seizures including status epilepticus, which can be life threatening. Risk of premature death including SUDEP (sudden unexpected death in epilepsy) is elevated in patients with Dravet syndrome. Additionally, the majority of patients will develop moderate to severe intellectual and development disabilities and require lifelong supervision and care.

What is Lennox‑Gastaut syndrome?

The onset of LGS typically occurs between ages of 3 to 5 years and can be caused by a number of conditions, including brain malformations, severe head injuries, central nervous system infections and genetic neuro-degenerative or metabolic conditions. In up to 30 percent of patients, no cause can be found. Patients with LGS commonly have multiple seizure types including drop and convulsive seizures, which frequently lead to falls and injuries, and non-convulsive seizures.

Resistance to anti-epileptic drugs (AEDs) is common in patients with LGS. Most patients with LGS experience some degree of intellectual impairment, as well as developmental delays and aberrant behaviours.