In Juneâ€”and for the first time everâ€”the FDA announced it had approved a drug containing an active ingredient found in cannabis. The ingredient is cannabidiol, or CBD, a compound that affects users differently than the commonly thought of â€śhighâ€ť that comes from marijuanaâ€™s tetrahydrocannabinol (THC) component. The freshly approved drug is Epidiolex, a strawberry-flavored, pharmaceutical-grade, purified CBD syrup used to treat patients who suffer from Dravet syndrome and Lennox-Gastaut syndrome (LGS), both traditionally difficult to treat forms of epilepsy.Â
A product of U.K.-based GW Pharmaceuticals and its U.S. subsidiary, Greenwhich Biosciences, Epidiolexâ€”currently a Schedule 1 substance in accordance with the parent plant of its key ingredientâ€”appears to bring hope to families who have long been seeking treatment options in accordance with these rare, severe, early-onset conditions.Â
Just what is Epidiolex, what do we know about the conditions it treats, what happened in clinical trials to warrant FDA approval and what does such approval mean for the overall state of the medical cannabis market? Laboratory Equipment talked with Stephen Schultz, Vice President, Investor Relations, GW Pharmaceuticals, to learn more.
Epidiolex and clinical trials
The Epidiolex development program began with a single patient whose parents had read some anecdotal evidence of CBD artisanal products helping reduce convulsive seizures in patients. That anecdotal evidence led to the first patient, and that push expanded to over 1,000 who currently receive medication at no charge through the FDAâ€™s Compassionate Use Access, a program designed to assist patients who are out of options. The program has been in place since 2013 and runs in parallel to pivotal studies that inform the new drug application for the safety and efficacy of the drug in question. The drug in question, in this case, is Epidiolex.
How does Epidiolex work? They donâ€™t fully understand the mechanism of action yet, Schultz said, but itâ€™s continually explored.
â€śWe believe itâ€™s multi-faceted,â€ť he said. â€śPerhaps one of those mechanisms has to do with inflammation management and perhaps one has to do with calcium synaptic channel modulation. Weâ€™re still elucidating that.â€ť
Still, Schultz said, itâ€™s clear Epidiolex works on a systemic levelâ€”something unique to cannabidiol medications, and something well-suited to treat epileptic conditions, particularly those in which the cause of the seizures are unknown. In such instances, a drug that affects the human system as a whole (rather than having a target point in the body) can have a significant impact on the quality of life of those living with these conditions because they may be beneficially affected by the systemic modulations. Thatâ€™s important because more than 90 percent of patients with Dravet syndrome or LGS suffer from at least one seizure per day. Letâ€™s take a closer look at both conditions and the clinical trial process for each.Â
Dravet syndrome is a type of epileptic encephalopathy that is associated with SCN1A sodium channel mutations. It affects over 5,400 people under 20 years of age in the U.S. alone. As the condition progresses, patients may suffer from multiple types of seizuresâ€”many of which, such as status epilepticus, can be long lasting and life threatening. Patients with this condition can suffer from behavioral disturbances, developmental delays, intellectual disability and more.
Until the approval for Epidiolex, there were no FDA-approved medications in the U.S. for treating Dravet syndrome. As such, the drugâ€”which received the formal orphan designationâ€”was fast-tracked to allow for an abridged review period. In Phase 2 trials, 34 patients from the U.S. and U.K. were randomized and received the drugâ€”or a placeboâ€”at various dosages over a course of four weeks. After a 10-day taper, they followed up with four additional weeks of treatment. Results published in the New England Journal of Medicine showed a dose of 20/mg/kg (coupled with standard treatment for epilepsy) decreased patient seizures by 39 percentâ€”a 26 percent increase over the placebo group.
The results were further explored during a similarly structured 120-person Phase 3 trial. In this trial, 43 percent of patients experienced a more than 50 percent reduction in convulsive seizures, and almost twice as many caregivers said the patientsâ€™ condition improved while taking Epidiolex (compared to the placebo). Adverse effects included diarrhea, decreased appetite, vomiting, pyrexia and others, but the treatment was generally well tolerated.
LGS can be caused by severe head injuries, brain malformations, infections of the nervous system and other issuesâ€”although in 30 percent of patients, there is no known causeâ€”and it generally initially affects children between the ages of 3 and 5. LGS patients often suffer drop seizuresâ€”defined by researchers as â€śatonic, tonic or tonic-clonic seizures involving the entire body, trunk or head that led or could have led to a fall, injury, slumping in a chair or hitting the patientâ€™s head on a surface.â€ť Patients often experience developmental and intellectual disabilities and require lifelong care.
During the trials for LGSâ€”the results of which were published in The Lancetâ€” researchers randomized 171 participants and administered either Epidiolex or a placebo in order to determine the efficacy of the drug on drop seizures and other symptoms. Trial participants ranged in age from 2 to 55 and were suffering from a median of 74 drop seizures per month. Ultimately, patients taking Epidiolex saw a 50 percent reduction in the number of monthly drop seizures compared to those taking the placebo alone, and the overall number of seizures suffered was reduced by 41 percent as well. Some patients did experience adverse effects similar to those felt by Dravet syndrome patients; 12 patients discontinued their treatment because of these effects, but they were resolved by the end of the 14-week study for 61 percent of those taking Epidioelx. One fatal case of acute respiratory distress syndrome was reported but was determined to be unrelated to the medication.
Overall, the trial found Epidiolex, when used in conjunction with other applicable anticonvulsant therapies, was effective in decreasing the number of drop and other seizures compared to the placebo and was generally well tolerated.Â
The state of the medical cannabis market
What makes Epidiolex different from going to a dispensary (in an area where they are, of course, legal) and purchasing CBD oil? The benefit, Schultz says, it the drugâ€™s pharmaceutical-grade statusâ€”and all that comes with it.
â€śYou donâ€™t know what youâ€™re buying at the dispensary level, and the results when these products are tested are disconcerting at best,â€ť Schultz said. â€śItâ€™s widely known THC levels and CBD levels tend to vary in most cases quite dramatically in these places. With an FDA approval, you get the confidence that what youâ€™re giving the patient has instructions based on clinical experience and has a fully characterized safety profile that guides the physicianâ€”something especially in polytherapy environments.â€ťÂ
Moreover, Schultz said he expects the DEA to change Epidiolexâ€™s classification from a Schedule 1 to one thatâ€™s less restrictive, such as a Schedule 4 or 5, given the finding the drug has very little abuse potential. That official decision is forthcoming. In the meantime, GW Pharmaceuticals and Greenwhich Biosciences are looking to expand Epidiolex into treatment of other conditions, as they will soon see results from Phase 3 trials for Tuberous Sclerosis Complex and infantile seizures. Theyâ€™re also commencing trials within their pipeline of CBD-based products to include those that treat autism spectrum disorders, Rhett syndrome, schizophrenia and glioblastoma.Â