GW’s pipeline in the field of epilepsy is currently focused on cannabidiol or CBD where we have an approved product in both the U.S. and Europe (EPIDIOLEX® in the US and EPIDYOLEX® in the EU/UK).
Multiple Sclerosis Spasticity
Our proprietary complex botanical mixture, called Sativex® (nabiximols in the US) is an oromucosal spray of a formulated cannabis extract that contains the principal cannabinoids delta-9-tetrahydrocannibinol (THC) and cannabidiol (CBD) as well as specific minor cannabinoids and other non-cannabinoid components. GW developed Sativex® to be administered as an oromucosal spray, whereby the active ingredients are absorbed in the lining of the mouth, either under the tongue or inside the cheek. Regulatory approval has been obtained in numerous countries outside the United States for the treatment of spasticity (muscle stiffness/spasm) due to MS.*
GW is now progressing a development program of nabiximols in the U.S. for the treatment of spasticity due to multiple sclerosis and has commenced a pivotal program in the U.S. designed to bridge from the previously conducted trials in Europe with the goal of submitting a New Drug Application (NDA) with the FDA for this indication. Importantly, other elements necessary for an NDA submission are largely in place. For example, we have nearly 100,000 patient years of safety data, as well as a regulatory-approved, commercial scale manufacturing process that has been in place for many years.
GW believes that there could be the potential for application for the broader spasticity market beyond multiple sclerosis as there are around three million patients in the United States with spasticity associated with various conditions. To this end, GW expects to also execute a clinical program in spasticity due to spinal cord injury. Beyond spasticity, GW has selected post-traumatic stress disorder (PTSD) as an additional target indication for the development of nabiximols.
Autism Spectrum Disorder (ASD)
Many of the childhood-onset intractable epilepsy conditions within the expanded access program share considerable overlap with ASD and these conditions often fall within the orphan disease space. Initial clinical observations from treating physicians suggest a potential role for cannabinoids in addressing problems associated with ASD such as deficits in cognition, behavior, and communication.
GW has evaluated the cannabinoids CBD and CBDV in both general and syndromic pre-clinical models of ASD yielding promising signals on cognitive and social functioning endpoints as well as repetitive behaviors.
At this time, GW’s clinical program in ASD is focused on the use of CBDV, which includes both open-label and investigator-led studies.
GW is continuing its clinical evaluation of CBD with a current focus on Rett Syndrome. The Company believes, based on promising pre-clinical data and observations from the Company’s pivotal and expanded access studies, that CBD offers potential in treating the non-seizure aspects of treatment-resistant epilepsy and commonly associated with ASD, such as cognitive deficits and behavioral challenges. These comorbidities are also typically seen in patients with Rett syndrome. GW considers its approved CBD formulation to be the most rapid development path for a potential treatment for patients with this challenging condition and is now recruiting a placebo-controlled Phase 3 trial.
Schizophrenia is a chronic disease that manifests through disturbances of perception, thought, cognition, emotion, motivation and motor activity. Over a lifetime, about 1% of the population will develop schizophrenia.
GW’s cannabinoids have shown notable anti-psychotic effects in pre-clinical models of schizophrenia and in September 2015, we announced positive top line results from an exploratory Phase 2a placebo-controlled clinical trial of a CBD formulation in 88 patients with schizophrenia who had previously failed to respond adequately to first line anti-psychotic medications. In this study, our CBD formulation demonstrated significantly reduced positive symptoms and significantly improved the clinical global impression of improvement, compared to placebo.
GW is now moving forward with a follow-on phase 2b placebo-controlled study aimed at further estimating the magnitude of the treatment effect of an investigational CBD-containing product on positive, negative and general symptoms of schizophrenia. We expect to initiate enrollment in mid-2020.
Neonatal Hypoxic-Ischemic Encephalopathy (NHIE)
NHIE is acute or sub-acute brain injury due to asphyxia caused during birth resulting from deprivation of oxygen during birth (hypoxia) as a result of a sentinel event such as ruptured placenta, parental shock and even increased heart rate. Hypoxic damage can occur to most of the infant’s organs, but brain damage is the most serious and least likely to heal, resulting in encephalopathy. This can later manifest itself as either mental retardation (including developmental delay and/or intellectual disability) or physical disabilities such as spasticity, blindness and deafness. The exact timing and underlying causes of these outcomes remains unknown but it is widely recognized that interventions need to be administered within six hours of hypoxic insult.
Under an IND, GW has completed a Phase 1 trial in healthy volunteers for an intravenous CBD formulation in the treatment of NHIE. After consulting with the FDA on the most appropriate design for an efficacy and safety study in neonates, the Company has commenced a safety study of our intravenous CBD formulation in NHIE in neonate patients in the US. There are currently no FDA-approved medicines indicated for NHIE.
GW has received Orphan Drug Designation and Fast Track Designation from the FDA for CBD for the treatment of NHIE. GW has also received Orphan Drug Designation from the EMA for CBD for the treatment of perinatal asphyxia, an alternate term that describes the same condition.
*See SmPC for full prescribing & safety information.