COWEN COLLABORATIVE INSIGHTS
Figure 125 GWPCARES3: Reduction In Drop Seizures
February 25, 2019
month and the average age of patients in the trial was 16 yrs, although 30% were 18 yrs or older. On the primary endpoint, 20 mg/kg Epidiolex produced a median reduction in monthly drop seizures of 42% compared to a reduction of 17% in patients taking placebo, p=0.0047. There was also a suggestion of a dose response in the data, with the lower 10 mg/kg/day dose of Epidiolex producing a median reduction in monthly drop seizures of 37%, p=0.0016. In both dose groups the difference between Epidiolex and placebo emerged during the first month of treatment and was sustained during the entire treatment period. GW disclosed that the trial's secondary endpoints, and a series of sensitivity analyses, confirmed the robustness of the results. Similar to Epidiolex's other Phase Ill studies, although patients on clobazam (51%) had some additional benefit, GW indicated that Epidiolex also showed efficacy in patients not on clobazam.
Figure 126 GWPCARE3: Responder Analysis
a
ut ¥ a4 t A a5 530 ; 3 3 25 . Ba} : Fas Ty 3" 25
Treatment Period (Primary)
Maintenance Period
ra Treatment Period 70 Maintenance Period MCBD 20 mglig (n=78) sen 94 — a ; CBD 10 mgikg(n=73) ——tpet).005 60 ‘pens eo pa PLB (n=78) a §pe0.001 50 50 F Baseline median (@1, Q3) drop seizure frequency: = CBD 20 mg/kg: 88 (38, 162) -* 7: hi : CBD 10 mglkg: 87 (41, 190) fs & ' Placebo: 80 (48, 148) * : - a 2 20 . Estimated treatment differences vs placebo a i ‘ti 13 * CBD 20 mg/kg: -21.6 (25% Cl: -34.8, -6.7) : i CBD 10 mg/kg: -19.2 (95% Cl: -31.2, -7.7) a en oH ae g == = =e
@ CBD 20 mg/kg (n=/6) CBD 10 mg/kg (n=73) PLB (n=76)
Source: GW Pharma, AAN 2017
90
Source: GW Pharma, AAN 2017
Additional data were presented at AAN 2017. Included in this presentation were several
of the trial's secondary endpoints and a series of sensitivity analyses. All of these confirmed the robustness of the results. For example, the proportion of patients witha >50% reduction in seizure frequency was 40% for 20 mg/kg Epidiolex (p<0.001), 36% for
10 mg/kg Epidiolex (p<0.01), and 15% for placebo. The proportion of patients with a >75% reduction in seizure frequency was 25% for 20 mg/kg Epidiolex (p<0.01), 11% for 10 mg/kg (p<0.05) Epidiolex, and 3% for placebo. The proportion of patients who
achieved seizure freedom was 7% for 20 mg/kg Epidiolex, 4% for 10 mg/kg Epidiolex,
and 1% for placebo.
Figure 127 GWPCARES3: Safety
CBD 20 mg/kg (n=82)
CBD 10 mg/kg (n=67)
Placebo (n=76)
mi (%) mi (%) ni (%) Al-causality TEAEs 7? (94) 56 (84) 55 (72) Treatment-related TEAEs 51 (62) 20 (30) 15 (20) TEAEs leading to withdrawal 6 (f) 1 (1.5) 1(1) Serious TEAEs 13 (16) 13 (19.4) 8 (11) Treatment-related serious TEAEs 5 (6) 2 (3) it) TEAESs reported in >10% of patients in any group by preferred term Somnolence 25 (31) 14 (21) 4(5) Decreased appetite 21 (26) 11 (16) 6 (8) Diarrhea 12 (15) F (10) 6 (8) Upper respiratory tract infection 11 (14) 11 (16) 11 (75) Pyrexia 10 (12) 6 (9) 12 (16) Vomiting 10 (12) 4 (6) 912) Nasopharyngitis 9 (11) 3 (5) 57) Status epilepticus 4 (5) 7 (10) 3 (4)
Source: GW Pharma, AAN 2017
COWEN.COM
HOUSE_OVERSIGHT_024906