COWEN COLLABORATIVE INSIGHTS February 25, 2019
head ona surface). The primary efficacy endpoint of the trials was a comparison between Epidiolex and placebo in the percentage change in the monthly frequency of drop seizures during the 14 week treatment period (including 2 weeks of dose escalation) compared to the 4 week baseline period. Following the completion of the blinded portion of the trial, all patients were eligible to receive Epidiolex in an open label extension study.
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Figure 123 1st LGS Phase 3 Trial Design Figure 124 2nd LGS Phase 3 Trial Dose Ranging Design SSS 55S asks, }—— 44 Week analyse period’ ———-+} tip ts + 14week analysis period ——+! Upto ' Baseline | 2 weeks 12 weeks ' 10 days ' 4 weeks 1 tod i" Gbserwelion’ “t° “Fitration 1 cTeesbnent “| Taper i+ Baseline =~ 2weeks 14. 12 weeks. —_____.! 10 days Period Phase Phase | Period | Observation | Titration Treatment Taper
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Epidiolex 20 mg/kg (n=50) ie
Part A Complete Dose Selection Screening Randomization Open Label Extension
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Primary Endpoint: % change from baseline in monthly drop seizure frequency during the 14 week treatment period compared with the 4 week baseline period
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Part A Complete Dose Selection Screening Randomization
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Measures taken to ensure quality, reduce noise include: -Choice of primary endpoint -Daily IVRS
-Diagnosis verification -Investigator selection of responsible -Seizure count and description training and familiar parents Source: GW Pharma Source: GW Pharma
The first Phase Ill trial, patients were on an average of three AEDs, and had previously tried and failed an average of 6 other AEDs. Even on their baseline medications, the patients were experiencing a median baseline drop seizure frequency of 74 per month. The average age of patients in the trial was 15 years, although 34% were 18 years or older. On the primary endpoint, Epidiolex produced a median reduction in monthly drop seizures of 44% compared to a reduction of 22% in patients taking placebo (p=0.0135). Epidiolex reduced all seizures by 41% vs. a 14% reduction for placebo (p=0.0005), while the reduction in all seizures during the maintenance period was 45% for Epidiolex vs. 15% for placebo (p=0.0004). Similar to the Dravet trial, there was a clear separation between Epidiolex and placebo on percent reduction in drop seizure frequency across all magnitudes of reduction. In particular, 44% of Epidiolex patients had at least a 50% reduction in drop seizures, compared to 24% of patients taking placebo (p=0.0043). 58% of Epidiolex patients compared to 34% of placebo patients were rated as "slightly improved", “much improved" or “very much improved" on the Subject/Caregiver Global Impression of Change.
Epidiolex appeared to be well tolerated in the trial. 86% of patients on Epdiolex had an adverse event, compared to 69% of placebo patients. The most common adverse events were diarrhea (19% of patients on Epidiolex vs. 8% of placebo patients), somnolence (15% vs. 9%), pyrexia (13% vs. 8%), decreased appetite (13% vs. 2%) and vomiting (11% vs. 17%). Again, there was no difference in the number of patients who experienced status epilepticus between Epidiolex (n=1) and placebo (n=1). There was one death in the Epidiolex group from acute respiratory distress syndrome, but it was not considered treatment related. Increases in ALT or AST (>3xULN) occurred in 20 CBD and 1 placebo patient, all of whom were on concomitant valproic acid. All elevations resolved.
In September 2016, GW announced that Epidiolex's second Phase III pivotal trial (GWPCARE3) in the treatment of Lennox-Gastaut syndrome was also successful. On
average, patients were on 3 AEDs at baseline, having previously tried and failed a mean of 7 other AEDs (median=10). The median baseline drop seizure frequency was 85 per
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