PracticeUpdate Neurology Best of 2018

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FDA Approval of Cannabidiol for Use in Lennox-Gastaut and Dravet Syndromes By Nina F. Schor MD, PhD

of hypoperfused tissue around the core infarct. Now, the triply revolutionized care of stroke involves rapid intervention (IV tPA and/or ET) given in well-organized, certi- fied stroke centers around the world. It is likely that the coming years will reveal that intervention can be effective even days after stroke in subsets of patients with persistent areas of hypoperfused tissue surrounding the ischemic core. But even the current management has resulted in higher functional outcomes for thousands of stroke patients each year. References 1. Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med 2018;378(8):708-718. 2. Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med 2018; 378: 11-21. www.practiceupdate.com/c/73543 Unlike tetrahydrocannabinol or THC, can- nabidiol does not bind to CB1 receptors and therefore does not cause euphoria or intoxication. 2 The cumulative experience of individual-investigator, open-label studies of cannabidiol in 214 patients with Len- nox-Gastaut and Dravet syndromes and other causes of treatment-resistant epi- lepsy demonstrated a 36.5% decrease in seizure frequency. A state-sponsored T he approval by the FDA in June 2018 of Epidiolex (cannabidiol) as an anti-seizure drug in patients with Lennox-Gastaut and Dravet syndromes is remarkable in several ways. 1 First, Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from marijuana. The FDA will doubtless need to withstand the public stigma of endorsing the use of a marijuana derivative as a med- ication. Second, Epidiolex is the first drug approved by the FDA for Dravet syndrome. The FDA is to be greatly commended for taking action on behalf of children with intractable seizures and intellectual disa- bility. Third, this drug of stigmatized origin to be used in a stigmatized pair of condi- tions is aimed at improving the lives and function of a frequently marginalized pop- ulation – young children.

study of adults and children with treat- ment-resistant epilepsy demonstrated significant reduction in seizure frequency that exceeded 50% in half of the patients. One study in children with tuberous sclero- sis demonstrated a durable 50% reduction in seizure frequency. 3 GW Pharmaceuticals, the manufacturer of Epidiolex, has sponsored four rand- omized, controlled trials of that drug in patients with treatment-resistant epilepsy syndromes, including Lennox-Gastaut and Dravet syndromes and tuberous sclerosis. Dose-dependent reductions in seizure frequency were as high as 42%. Adverse effects were largely mild or mod- erate, often transient, and most commonly included somnolence and diarrhea. 3 The availability of a potentially efficacious drug for treatment-resistant epilepsy is an advance in and of itself. But the most significant impact of the FDA’s approval of Epidiolex for patients with syndromes marked by treatment-resistant epilepsy may be the demarginalization of these patients and the destigmatization of their disease. References 1. US Food and Drug Administration. FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy [press release]. Silver Spring, MD. US Depart of Health and Human Services; 2018. 2. Nahler G, Grotenhermen F, Zuardi AW, Crippa JAS. A conversion of oral cannabidiol to delta9-tetrahydrocannabinol seems not to occur in humans. Cannabis Cannabinoid Res 2017;2(1):81-86. 3. O’Connell BK, Gloss D, Devinsky O. Cannabinoids in treatment-resistant epilepsy: A review. Epilepsy Behav 2017;70(Pt B):341-348. www.practiceupdate.com/c/74531

24 hours after stroke. These results sub- stantially increased the window of time for effective treatment and led to the third major revolution in the treatment of acute ischemic stroke. The first revolution in stroke care, more than 2 decades ago, occurred when a large randomized clini- cal trial showed that IV tPA given ≤3 hours post onset in patients with hemorrhage or early evidence of large infarct resulted in better functional outcomes compared with placebo. The second revolution occurred when several randomized clinical trials showed the benefit of ET (with or without IV tPA) up to 6 hours post onset in patients with large-vessel occlusion and small core infarct compared with IV tPA alone. Less than 25 years ago, there was essentially no medical intervention to limit expansion of the infarct in the early stages of stroke, despite evidence from animal studies obtained decades earlier that infarcts expanded into the larger area " …thisdrugof stigmatizedorigin to be used in a stigmatized pair of conditions is aimed at improving the lives and function of a frequently marginalized population – young children. "

VOL. 3 • NO. 4 • 2018