MGC Pharmaceuticals | 22 October 2018
8
syndrome and Lennox-Gastaut syndrome (LGS). The FDA approved Epidiolex for these two
disorders in June 2018. The company has also filed for approval in Europe.
GW has reported positive results from three Phase III studies in Dravet and LGS patients, as shown
in Exhibit 2. The average reduction in seizure frequency for Epidiolex doses of 10-20mg/kg in the
three studies ranged from 37-44%, compared to 13-22% for placebo.
Exhibit 2: Phase III trials of GW Pharmaceuticals’ Epidiolex in Dravet and LGS
Indication
Doses
tested
Number of
patients
Average
age
Average number
of AEDs currently
prescribed
Number of
previously
tried AEDs
Median baseline
seizure
frequency
Epidiolex
seizure
reduction
Placebo
seizure
reduction
p-value
Dropouts
due to AEs
Dravet
20mg/kg
120
10
3
4
13 convulsive
seizures
-39%
(20mg/kg)
-13%
0.0123
13%
LGS Trial 1
20mg/kg
171
15
3
6
74 drop seizures
-44%
(20mg/kg)
-22%
0.0135
14%
LGS Trial 2
20mg/kg
and
10mg/kg
225
16
3
7
85 drop seizures
-42%
(20mg/kg),
-37%
(10mg/kg)
-17%
0.0047
(20mg/kg),
0.0016
(10mg/kg)
8%
(20mg/kg),
1%
(10mg/kg)
Source: Edison Investment Research, GW Pharmaceuticals
Transdermal CBD fails in adult epilepsy, highlighting clinical risk remains
Despite the proven efficacy of CBD in severe forms of epilepsy, the failure of Zynerba’s CBD gel in
adult epilepsy shows there is no certainty that a particular product or clinical trial will deliver a
positive result.
Zynerba, which has been developing ZYN002, a synthetic transdermal cannabidiol gel for adult
epilepsy patients with focal seizures, announced that the compound failed to show significance in
any of the primary or secondary endpoints in its Phase II trial (known as STAR 1). Whereas
Epidiolex was able to show a ~40% reduction in seizure frequency in its three Phase III trials,
ZYN002 was only able to show an 18.4% reduction at the lower dose (195mg daily total) and a
14.0% reduction at the higher dose (390mg daily total).
Other new epilepsy drugs on the horizon
In September 2017, Zogenix announced positive Phase III results for ZX008 (fenfluramine) in
treatment-resistant Dravet Syndrome. The responder rate (at least 50% reduction in seizures) was
75% for the high dose, 41% for the low dose and 7.5% on placebo. In a confirmatory Phase III
reported in July 2018, the responder rate for an intermediate dose was 54% for ZX008 vs 7% for
placebo. If it is approved ZX008 is likely to compete with cannabinoid drugs for market share.
The severe refractory epilepsy market
Epilepsy is a severe neurological disorder that is estimated to affect more than 70 million people
worldwide.
3
Based on a meta-analysis of epidemiology studies, Fiest et al calculated the average
prevalence of active epilepsy to be 6.4 patients with active epilepsy per 1,000 head of population.
4
Following a review of the epidemiology of epilepsy in Europe, Forsgren et al reported that ~20-30%
of patients experience at least one seizure per month.
5
Combining the higher 30% estimate of
patients with frequent seizures with the fact that one-third of patients have treatment-resistant
epilepsy (due to likely overlap between the two groups), we estimate that 10% of all patients with
active epilepsy have frequent seizures that are resistant to antiseizure drugs.
3
Ngugi et al. Incidence of epilepsy: a systematic review and meta-analysis. Neurology (2011) 77:1005–12.
doi:10.1212/WNL.0b013e31822cfc90.
4
Fiest et al. Prevalence and incidence of epilepsy. Neurology 2017;88:296–303
5
Forsgren et al. The epidemiology of epilepsy in Europe…European Journal of Neurology 2005, 12: 245–253