New research published March 2, 2020, in the journal JAMA Neurology confirmed prior study outcomes demonstrating the effectiveness of this oral medication for Dravet syndrome at a dose of 20 milligrams per kilogram (mg/kg) per day. (The drug, which comes in a sesame oil with strawberry flavoring, is given according to a child’s weight.)
Results Show That a Lower Dose Is Safe, Effective
“This is the first study, however, to show efficacy and safety for a 10 mg/kg a day dose in these patients,” says lead investigator Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami. “It will not change the FDA indication, but will inform physicians regarding optimizing the benefit-risk ratio for patients.” The trial, which included 199 patients ages 2 to 18 with a confirmed diagnosis of Dravet syndrome, showed that the 10-mg dose may be just as effective as the 20-mg dose. Scientists discovered that those taking 10 mg experienced seizure reductions of 49 percent compared with 46 percent reduction in those taking 20 mg and a 27 percent reduction for those on placebo. Stephen Schultz, the vice president of investor relations for GW Pharmaceuticals, which makes Epidiolex, indicates that the results should give physicians greater flexibility when it comes to dosing. “For some patients, the 10 [mg] will work well, but others will be more resistant and will need more,” he says.
Notoriously Resistant to Treatment
Dravet syndrome is a rare, catastrophic form of lifelong epilepsy that affects about 1 in every 15,700 individuals in the United States, according to the Dravet Syndrome Foundation. This severe epilepsy can bring on frequent, prolonged seizures often triggered by high body temperature (hyperthermia), as well as developmental delay, speech impairment, ataxia (a degenerative disease of the nervous system), hypotonia (decreased muscle tone), sleep disturbances, and other health problems. So far, the condition has been extremely challenging to treat, with response to medication being inadequate. The participants in this investigation were taking multiple anticonvulsants, such as levetiracetam, divalproex, topiramate, zonisamide, ethosuximide, and clobazam. “Even with these currently available treatments, only about 10 percent of patients with Dravet syndrome achieve adequate seizure control,” says Dr. Miller. A report published in September 2019 the journal CNS Drugs, however, highlighted new therapies — including stiripentol, fenfluramine, and cannabidiol — which have produced promising results in reducing convulsive seizure frequency. Greenlighted by the FDA for Dravet syndrome treatment in June of 2018, Epidiolex is the first prescription pharmaceutical formulation of a highly purified, plant-derived cannabinoid — but without the “high” associated with marijuana. “This study is not necessarily providing new information but providing further evidence of the usefulness of Epidiolex in Dravet Syndrome,” says Melissa L Bernbaum, MD, director of neurology at Northwell Health’s Huntington Hospital in Huntington, New York. She adds that, while there may be a stigma attached to cannabidiol because of the medication’s connection with marijuana, she does not have any patients with such concerns at her practice and in fact, many are interested in “medical marijuana.” “Parents actually tend to have a positive emotional reaction to the fact that the medication is produced from a plant and then purified, rather than being synthesized in a test tube,” says Miller. With the benefits of cannabidiol being scientifically proven, GW Pharmaceuticals is seeking the FDA’s thumbs-up for Sativex (naximbols), a spasticity treatment for patients with multiple sclerosis that contains two chemical extracts derived from the cannabis plant. The product is currently approved in 29 countries outside the United States, according to the company. The company is also exploring cannabinoid-based therapies for autism, spinal cord spasticity, schizophrenia, and post-traumatic stress disorder (PTSD).
Staying Alert to Possible Side Effects
Overall, Epidiolex has a favorable safety profile with notable side effects being the risk of liver enzyme elevations, appetite changes, diarrhea, somnolence (sleepiness), pyrexia (fever), and fatigue. “It is also important to note potential interactions with other anti-seizure medication,” says Dr. Bernbaum. “Certain combinations may be more likely to cause sedation.” Schultz stresses that dosing above 25 mg did not significantly improve seizure response, but did increase the number of adverse events. “Given that, it makes sense for the top end of dosing to be around 25 [mg],” he says. At this time, the sticker cost for the drug is not inexpensive. On average, the price for Epidiolex in the United States for the first year of use was in the $32,000 per year range, according to Schultz, who adds that the out-of-pocket copay may be no more than $25 per patient. Because dosing depends on patient’s weight, he points out that the product will cost less for young lighter patients and more for older heavier patients. “Physicians and patients desired a pharmaceutical formulation of a cannabinoid that has gone through proper clinical trials and been tested for safety and efficacy,” says Schultz. “With Epidiolex, they have one that is exactly the same every time that it is taken, and because it is FDA-approved, it will be paid for by insurance.”
