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HOUSE_OVERSIGHT_024904

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COWEN COLLABORATIVE INSIGHTS February 25, 2019 s Figure 121 Efficacy Results From Epidiolex’s First Phase Ill Trial In Dravet Syndrome A| Convulsive Seizures B| Total Seizures CBD (n-61) @ CBD (n=61) § Placebo (n=59) @ Placebo (n=59) 50) 50 45 p-0.0123 0.0052 = - 2 = * p-0.0234 = # = 35 2 30 2 30 eons ¢ 20 & 20 B 18 B ob = ae = 10 5 5 o|___d po Lae ° Treatment Period Maintenance Period Treatment Period Maintenance Period (Primary) 3 Source: GW Pharma, AES 2016 The most common adverse events were reported to be somnolence (36% in patients on Epidiolex vs. 10% in placebo patients), diarrhea (31% vs. 10%), decreased appetite (28% vs. 5%), fatigue (20% vs. 3%), pyrexia (15% vs. 9%), and vomiting (15% vs. 5%). Importantly, there was no difference in the number of patients who experienced status epilepticus between Epidiolex (n=4) and placebo (n=3). Increases in ALT or AST (>3x ULN) occurred in 12 CBD and 1 placebo patient, all of whom were on concomitant valproic acid. All elevations resolved. SAEs were seen in 10 Epidiolex patients vs. three on placebo. Eight patients on Epidiolex discontinued treatment compared with one patient on placebo, due to adverse events similar to those above, including three due to ALT/AST elevations. Figure 122 Safety Data From Epidiolex’s First Phase III Trial In Dravet Syndrome | CBD(n=61) | Placebo (n=59) n(%) n(%) All-causality TEAES 44(74.6%) Treatment-related TEAEs 16(27.1%) TEAEs leading to withdrawal 1(1.7%) Serious TEAEs 315.1%) TEAEs reported in >10% of patients in either group by preferred term Somnolence 6(10.2%) Upper respiratory trac infection 5(85%) Source: Cowen and Company In 2015, GW initiated two Phase Ill trials in Lennox-Gastaut Syndrome. The first trial enrolled 171 patients, and the second enrolled 225. In the first LGS study, the patients were randomized 1:1 to 20mg/kg or placebo while in the second, they were randomized 1:1:1 to 20mg/kg Epidiolex, 10mg/kg Epidiolex, or placebo. The LGS trials assessed drop seizures (a

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