Epilepsy is estimated to affect 50 million people worldwide including, according to the Centers for Disease Control and Prevention, 2.2 million people in the United States. Epilepsyi is a serious neurological disorder typically manifesting as spontaneous convulsions and/or a loss of consciousness.

Epilepsy carries long term health implications such as cognitive deficits, mental health problems  and physical (sclerotic) damage to affected areas, particularly in children. Epilepsy symptoms are caused by the appearance of abnormal electrical seizure discharges and are characterised by episodic high frequency neuronal firing within various brain areas. Seizures are frequently a result of excitatory and inhibitory synaptic imbalances and usually begin (and may remain confined) to a specific area and/or spread to other regions of the brain.


The specific cellular, molecular and genetic mechanisms underlying the many forms of this disorder are still poorly understood, particularly in the infant, paediatric and juvenile populations where it is most prevalent (10.5m global casesii) and may vary significantly from individual to individual. Furthermore, anticonvulsant therapies are associated with significant cognitive side-effects, toxicity, unknown effects on brain development and a serious lack of seizure control at therapeutic dosesiii. The development of both in vitro and in vivo animal models of epilepsy permits the reproduction of specific seizure discharge features seen in human clinical cases, allows for a better understanding of the disease state and aids the development and screening of more effective anticonvulsant agents.


Drug therapy remains ineffective for seizure control in up to 30% of patients with epilepsy because either the drugs do not control the seizures or the patients cannot tolerate the side effects. Currently available drugs can cause significant side effects to individuals’ movement and cognitive abilities that can adversely affect the quality of life for epileptic patients.


GW’s pipeline in the field of epilepsy includes the following two product candidates:



A liquid formulation of pure plant-derived Cannabidiol (CBD), as a treatment for various orphan pediatric epilepsy syndromes, for which FDA has granted Orphan Drug Designation in the treatment of Dravet syndrome and Lennox-Gastaut syndrome and Fast Track Designation for Dravet syndrome; and



Which features Cannabidivarin (CBDV) as the primary cannabinoid and which has shown antiepileptic properties across a range of pre-clinical models of epilepsy. GW has advanced CBDV into a Phase 2 study of 130 patients with epilepsy.
CBDV strongly suppressed seizures in six different experimental models commonly used in epilepsy treatment
Phase 1 study completed in 66 healthy subjects, CBDV tolerated even at the highest tested dose and no serious or severe adverse events, nor any withdrawals due to AEs.



i. Sander, J.W. (2003). The epidemiology of epilepsy revisited. Curr Opin Neurol, 16, 165-70.

ii. Guerrini, R. (2006). Epilepsy in children. Lancet, 367, 499-524.

iii. Suchomelova, L., Baldwin, R.A., Kubova, H., Thompson, K.W., Sankar, R. & Wasterlain, C.G. (2006). Treatment of experimental status epilepticus in immature rats: dissociation between anticonvulsant and antiepileptogenic effects. Pediatr Res, 59, 237-43.



Orphan Pediatric Epilepsy Program

Epilepsy is one of the most common neurological disorders in children. According to Russ in the February 2012 edition of Pediatrics, there is a point prevalence of 6.3 per 1,000 children currently diagnosed with epilepsyi. Based on these findings, we estimate that 466,000 childhood patients in the United States and 765,000 patients in Europe are currently diagnosed with epilepsy.


It is estimated that up to 30% of these cases show pharmacoresistance to current treatment (i.e., seizures that persist despite accurate diagnosis and carefully monitored treatment with multiple antiepileptic drugs) and are deemed 'medically intractable'ii iii. Furthermore it is recognized that some of those that do find relief often suffer side effects severe enough with their current medication that an alternative or adjunct is often sought.


In total, therefore, we believe the size of the intractable pediatric epilepsy population is approximately 140,000 patients in the United States and 230,000 in Europe.



i. Russ SA, Larson K, Halfon N. A National Profile of Childhood Epilepsy and Seizure Disorder. Pediatrics. 2012 Feb;129(2):256-64.


ii. Wirrel EC. Predicting pharmacoresistance in pediatric epilepsy. Epilepsia,2013: 54(Supp. S2):19-22



Epidiolex (CBD) Development Strategy in Pediatric Epilepsy

GW’s strategy for the development of Epidiolex in pediatric epilepsy is to initially concentrate on two orphan indication syndromes—Dravet Syndrome and Lennox-Gastaut Syndrome, or LGS. GW has received from the U.S. Food and Drug Administration Orphan Drug Designation for Epidiolex for the treatment of Dravet syndrome and Lennox-Gastaut syndrome and has received Fast track Designation for Dravet syndrome. GW expects to further expand the market opportunity by either targeting additional orphan seizure disorders and/or by seeking approval for a wider indication of pediatric epilepsy refractory to current treatments and has annonced plans to develop Epidiolex in a third target indication, Tuerous Sclerosis Complex, a rare pediatric genetic disorder, the most common symptom of which is epilepsy .




GWP42006 (CBDV) in Epilepsy

In addition to CBD, GW has a second product candidate, GWP42006, which features CBDV as the primary cannabinoid, which has also shown anti-convulsant effects across a range of in vitro and in vivo models of epilepsy. CBDV is similar in chemical structure to CBD.


In a paper published in the September 2012 issue of The British Journal of Pharmacology by scientists with whom we collaborate at the University of Reading, United Kingdom, GWP42006 was reported to have the potential to prevent more seizures, with few of the side effects caused by many existing anti- epileptic drugs, such as uncontrollable shaking. In the study, GWP42006 strongly suppressed seizures in six different experimental models commonly used in epilepsy treatment. GWP42006 was also found to provide additional efficacy when combined with drugs currently used to control epilepsy.


Recent studies have shown that within rats exposed to PTZ to induce seizure, brain levels of mRNA is increased in genes encoding proteins responsible for neuronal activity and plasticity; synaptic plasticity; and genes encoding inflammatory markers and nerve growth factors. It was demonstrated that for animals who responded to GWP42006, and whose seizure subsided, gene expression was reduced back to normal, whereas the level of mRNA in those animals that failed to respond to GWP42006 treatment remained high. This provided direct genetic biomarker evidence supporting previously reported work showing GWP42006’s ability to reduce seizures in mice and rats.


GWP42006 has the potential for development in the field of pediatric epilepsy as well as the broader epilepsy market.


GW is investigating the potential for cannabinoids as anti-epileptic treatments in collaboration with researchers at the University of Reading. One of the techniques used by the team is to examine the antiepileptiform potential of cannabinoids using in vitro multielectrode array (MEA) extracellular electrophysiologic techniques on brain slices. A low magnesium ion saline solution or a 4AP (4-aminopyridine; a pro-convulsant) containing medium can trigger burst discharges that are synchronised throughout large cell populations in hippocampal or periform cortical slice cultures. These appear essentially identical to those evoked in vivo. By studying the impact of cannabinoid addition on the amplitude of the epileptiforms produced, researchers are able to recognise if our compounds could perform as an anti-epileptic drug in vivo.


and has announced that plans to develop Epidiolex in a third target indication, Tuberous Sclerosis Complex, a rare pediatric genetic disorder, the most common symptom of which is epilepsy.


 Cannabinoid Publications in Epilepsy


Epidiolex (Cannabidiol) in Treatment Resistant Epilepsy

Orrin Devinsky1, Joseph Sullivan2, Daniel Friedman1, Elizabeth Thiele3, Eric Marsh4, Linda Laux5, Ian Miller6, Robert Flamini7, Angus Wilfong8, Francis Filloux9, Matthew Wong10, Nicole Tilton2, Patricia Bruno3, Rebecca Kamens4, Jane Maclean4, Judith Bluvstein1, Srishti Nangia5, Anup Patel11, Maria Roberta Cilio2

1NYU Epilepsy Center, 2UCSF Benioff Children’s Hospital, 3MassGeneral Hospital for Children, 4Children’s Hospital of Philadelphia, 5Lurie Children’s Hospital, 6Miami Children’s Hospital, 7Pediatric and Adolescent Neurodevelopmental Associates (Atlanta, GA), 8Texas Children’s Hospital, 9University of Utah Medical Center, 10Wake Forest School of Medicine, 11Nationwide Children’s Hospital


Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy.

Porter BE, Jacobson C. Epilepsy Behav. 2013 Dec;29(3):574-7.


Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression.

Amada N, Yamasaki Y, Williams CM, Whalley BJ. PeerJ. 2013 Nov 21;1:e214.


Cannabidivarin is anticonvulsant in mouse and rat.

Hill AJ, Mercier MS, Hill TD, Glyn SE, Jones NA, Yamasaki Y, Futamura T, Duncan M, Stott CG, Stephens GJ, Williams CM, Whalley BJ. Br J Pharmacol. 2012 Dec;167(8):1629-42.


Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures

Jones NA, Glyn SE, Akiyama S, Hill TD, Hill AJ, Weston SE, Burnett MD, Yamasaki Y, Stephens GJ, Whalley BJ, Williams CM.Seizure. 2012 Jun;21(5):344-52


Phytocannabinoids as novel therapeutic agents in CNS disorders

Hill AJ, Williams CM, Whalley BJ, Stephens GJ. Pharmacol Ther. 2012 Jan;133(1):79-97


Δ⁹-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats

Hill AJ, Weston SE, Jones NA, Smith I, Bevan SA, Williamson EM, Stephens GJ, Williams CM, Whalley BJ. Epilepsia. 2010 Aug;51(8):1522-32.


Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo

Jones NA, Hill AJ, Smith I, Bevan SA, Williams CM, Whalley BJ, Stephens GJ. J Pharmacol Exp Ther. 2010 Feb;332(2):569-77.


The phytocannabinoid Delta(9)-tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellum 

Ma YL, Weston SE, Whalley BJ, Stephens GJ. Br J Pharmacol. 2008 May;154(1):204-15.