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COLLABORATIVE INSIGHTS
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 III studies, although patients on clobazam (51%) had some additional benefit, GW indicated that Epidiolex also showed efficacy in patients not on clobazam.

Figure 125 GWPCARE3: Reduction In Drop Seizures

[Chart showing Reduction % reduction / 28 days]
Treatment Period (Primary)
Maintenance Period

Source: GW Pharma, AAN 2017

Figure 126 GWPCARE3: Responder Analysis

[Chart showing % Patients]
Treatment Period
Maintenance Period

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 with a >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 GWPCARE3: Safety

[Table Data]

| | CBD 20 mg/kg (n=82) n (%) | CBD 10 mg/kg (n=67) n (%) | Placebo (n=76) n (%) |
|---|---|---|---|
| All-causality TEAEs | 77 (94) | 56 (84) | 55 (72) |
| Treatment-related TEAEs | 51 (62) | 20 (30) | 15 (20) |
| TEAEs leading to withdrawal | 6 (7) | 1 (1.5) | 1 (1) |
| Serious TEAEs | 13 (16) | 13 (19.4) | 8 (11) |
| Treatment-related serious TEAEs | 5 (6) | 2 (3) | 0 |
| TEAEs 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) | 7 (10) | 6 (8) |
| Upper respiratory tract infection | 11 (14) | 11 (16) | 11 (15) |
| Pyrexia | 10 (12) | 6 (9) | 12 (16) |
| Vomiting | 10 (12) | 4 (6) | 9 (12) |
| Nasopharyngitis | 9 (11) | 3 (5) | 5 (7) |
| Status epilepticus | 4 (5) | 7 (10) | 3 (4) |

Source: GW Pharma, AAN 2017

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