By: Richard M. Blau, Chair, GrayRobinson’s Medical Marijuana Law Group
GW Pharmaceuticals plc (Nasdaq:GWPH), a biopharmaceutical company focused on commercializing novel therapeutics from its proprietary cannabinoid product platform, announced with its U.S. subsidiary, Greenwich Biosciences, that the Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) of the U.S. Food and Drug Administration (FDA) unanimously recommended supporting the approval of the New Drug Application (NDA) for the investigational cannabidiol oral solution (CBD), also known as Epidiolex® The recommendation, announced at an April 19th meeting of the PCNS, is focused on use for the adjunctive treatment of seizures associated with two particularly severe forms of epilepsy: (i) Lennox-Gastaut syndrome or "LGS;" and (ii) Dravet syndrome in patients two years of age and older.
If ultimately approved by FDA, Epidiolex would be the first pharmaceutical formulation of purified, plant-based CBD authorized by the federal agency, and the first in a new category of anti-epileptic drugs (AEDs).
LGS and Dravet syndrome, which develop in childhood, are devastating forms of epilepsy with high morbidity and mortality rates. Both forms of epilepsy produce significant burdens on families and caregivers, as well as patients. More than 90% of patients with LGS or Dravet syndrome have multiple seizures per day, which puts them at constant risk for falls and injury.
Physicians who treat LGS and Dravet syndrome patients struggle to reduce the sheer volume of dangerous seizures with currently available therapies. If approved, Epidiolex would be the first-ever FDA-approved medicine for Dravet syndrome patients.
The drug’s producers presented the results of a robust clinical development program that included three randomized, controlled Phase 3 clinical trials and an open-label extension study. In the Phase 3 studies, the combination of Epidiolex with other antiepileptic therapies significantly reduced the frequency of seizures in patients with LGS and Dravet syndrome.
The Epidiolex development program represents the only well-controlled clinical evaluation of a cannabinoid medication for patients with LGS and Dravet syndrome. Elizabeth Thiele, MD, PhD, director of pediatric epilepsy at Massachusetts General Hospital, professor of Neurology at Harvard Medical School and a primary investigator for one of GW’s and Greenwich’s studies in LGS patients, was quoted in published reports as stating: "The results from these studies suggest that this pharmaceutical formulation of cannabidiol may provide hope for a new treatment option that may be effective for some patients."
In reviewing the Epidiolex presentation, the PCNS members were provided an agency briefing memorandum that included the following points:
Cannabidiol (CBD) is a cannabinoid prepared from the Cannabis sativa L. plant and is a new molecular entity. It is structurally unrelated to other drugs approved for the treatment of seizures. CBD is currently a Schedule I drug. The exact mechanism of the anticonvulsant effect of CBD is unknown, but does not appear to involve an interaction with cannabinoid receptors.
Both LGS and DS are rare, severe, refractory epilepsy syndromes with onset in early childhood. The syndromes are categorized as developmental and epileptic encephalopathies, in which the epileptic activity is thought to contribute to developmental delay and behavioral abnormalities beyond the pathology of the underlying disease. The syndromes are characterized by multiple seizure types that are generally refractory to many of the drugs typically used for the treatment of seizures. Both syndromes are associated with higher rates of mortality than in the general epilepsy population, primarily due to status epilepticus and sudden unexpected death in epilepsy patients (SUDEP).1
Full FDA approval is still a long way off. FDA Advisory Committees are independent expert panels; their votes are not binding on the regulatory agency. Still, panel recommendations are considered by the FDA when deciding whether to approve a new medicine.
The full agenda of the PCNS’ April 19th meeting is accessible online at by visiting this link. The PDUFA (Prescription Drug User Fee Act) goal date for completion of the NDA review of the cannabidiol oral solution is June 27, 2018.
1 FDA Briefing Document: Peripheral and Central Nervous System Drugs Advisory Committee Meeting, NDA 210365 Cannabidiol (April 19, 2018); this document is accessible online via the FDA’s Website.