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COWEN
COLLABORATIVE INSIGHTS
February 25, 2019

Figure 128 Pooled LGS % Seizure Reduction: 10mg/kg Epidiolex vs. Placebo
[Chart Data: On CLB, On VPA, Off CLB, Off VPA - displaying percentages of seizure reduction for Placebo vs 10 mg/kg/d]
Source: GW Pharma, AES 2017

Figure 129 Pooled LGS % Seizure Reduction: 20mg/kg Epidiolex vs. Placebo
[Chart Data: On CLB, On VPA, Off CLB, Off VPA - displaying percentages of seizure reduction for Placebo vs 20 mg/kg/d]
Source: GW Pharma, AES 2017

GW has also studied CBD in psychiatric indications. Results from an exploratory study of CBD (GWP42003) in schizophrenia were released in September 2015. The trial was a Phase IIa 6 week, placebo-controlled exploratory trial in 88 patients with schizophrenia refractory to first line anti-psychotic medications. To be enrolled, patients must have been treated for a minimum of four weeks on a first line anti-psychotic medication and still have a PANSS total score in excess of 60. CBD was administered as adjunct therapy on a background of antipsychotic medication. The trial did not have a primary endpoint, but rather a number of exploratory endpoints.

CBD consistently demonstrated superiority to placebo, suggesting that CBD may have substantial anti-psychotic effects. CBD produced statistically significant benefits compared to placebo on the PANSS positive sub-scale (p=0.018), the Clinical Global Impression of Severity (p=0.04) and Clinical Global Impression of Improvement (p=0.02). The proportion of responders (improvement in PANSS Total score > 20%) was higher on CBD than placebo (p=0.07), with an Odds Ratio of 2.65. Moreover, CBD trended superior to placebo (p=0.07) on sub-domains of the PANSS that were particularly relevant to cognition in people with schizophrenia. The Scale for Assessment of Negative Symptoms showed a trend in favor of CBD, and reached statistical significance in patients taking CBD together with a leading first line anti-psychotic medication. The rest of the exploratory endpoints, many of which were other scales measuring functionality and cognition in schizophrenia patients, also trended in favor of CBD.

Even in the context of schizophrenia, CBD produced a clean safety profile, with no serious adverse events and a balanced incidence of adverse events compared to placebo. The most common adverse events were diarrhea (9.3% CBD vs. 4.4% placebo), nausea (7% CBD vs. 0% placebo), headache (7% CBD vs. 8.9% placebo) and somnolence (0% CBD vs. 6.7% placebo). There were two withdrawals from the study due to treatment-related adverse events, one each for CBD and placebo.

CBD's activity in schizophrenia is supported by pre-clinical data in animal models, as well as by a recent study published in The Journal of Clinical Investigations (2012) which suggested CBD may be usefully as either monotherapy or in combination with first line anti-psychotic agents. Nonetheless, while the p-values suggest that CBD has activity, its potency is difficult to judge without knowing the effect sizes. Therefore, additional data from this and subsequent studies will be necessary to fully understand the potential of CBD in schizophrenia. GW Pharma has indicated that it intends to pursue CBD's future development in pediatric orphan neuropsychiatric indications.

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