TIDMGWP
RNS Number : 1664K
GW Pharmaceuticals PLC
24 December 2015
The Lancet Neurology Publishes Data from the Epidiolex(R)
Expanded Access Program in Children and Young Adults with
Treatment-Resistant Epilepsy
London, UK; 24 December 2015: GW Pharmaceuticals plc (Nasdaq:
GWPH, AIM: GWP, "GW," "the Company" or "the Group"), a
biopharmaceutical company focused on discovering, developing and
commercializing novel therapeutics from its proprietary cannabinoid
product platform, today announced that Epidiolex(R) (cannabidiol or
CBD) data from the physician-led expanded access program in
treatment-resistant epilepsy were published in The Lancet
Neurology(1) .
The published paper reports that Epidiolex reduced seizure
frequency across multiple drug-resistant epilepsy syndromes and
seizure types and was generally well tolerated. The authors note
that the administration of Epidiolex as an add-on treatment led to
a clinically meaningful reduction in seizure frequency in many
patients and had an adequate safety profile in this patient
population with highly treatment-resistant epilepsies. The safety
and tolerability profile of Epidiolex was favorable with only 3
percent of patients terminating therapy due to an adverse event.
The authors note that without a control group, the results
regarding efficacy and safety should be interpreted cautiously.
"We are pleased that The Lancet Neurology has chosen to report
these promising data on a significant number of patients with very
challenging forms of epilepsy," said lead author Orrin Devinsky,
M.D., of New York University Langone Medical Center's Comprehensive
Epilepsy Center. "These data reinforce and support the safety and
efficacy we have shared in previous studies. Most importantly the
results are providing hope to the children and their families who
have been living with debilitating seizures. Further study is
needed before results can be confirmed and randomized controlled
studies are now underway to help us better understand the
effectiveness of the drug. We very much look forward to the results
from these studies in 2016."
The expanded access program is a non-placebo controlled
"compassionate access" program carried out by individual
investigators independent from GW. Patients enrolled in the
expanded access program were some of the most treatment-resistant
patients being treated at each of the epilepsy centers. Prior to
participating in the expanded access program, many of these
patients failed to achieve seizure control despite treatment with
antiepileptic drugs, dietary therapies, surgical therapies, and
vagus nerve stimulation. The median number of concomitant
antiepileptic drugs at the start of the trial was three. Data in
the paper are from 11 independent epilepsy centers in the U.S.; 162
patients who had at least 12 weeks of follow-up after the first
dose of cannabidiol were included in the safety and tolerability
analysis, and 137 patients were included in the efficacy analysis.
Of these 162 patients, there were 33 patients with Dravet syndrome
and 31 patients with Lennox-Gastaut syndrome (LGS). Dravet syndrome
and LGS are two rare, extremely debilitating epilepsy syndromes
that begin in infancy or early childhood. Ninety percent or more of
people with Dravet Syndrome and LGS are considered treatment
resistant.
The Lancet Neurology paper provides a more expansive description
of data previously presented at the American Academy of Neurology
Annual Meeting in April 2015. Since that time, additional expanded
access data, encompassing almost twice the number of patients, were
presented as a late-breaking poster at the American Epilepsy
Society Annual Meeting earlier this month(2) .
"We are pleased that these Epidiolex data were selected for
publication in The Lancet Neurology. The treatment effect seen in
this open label study of Epidiolex in our initial target
indications of Dravet syndrome and Lennox-Gastaut syndrome shows
consistency with other data disclosures, and also demonstrates the
effect of Epidiolex across multiple drug-resistant epilepsy
syndromes and seizure types," stated Justin Gover, GW's Chief
Executive Officer. "GW's Phase 3 pivotal safety and efficacy
studies in Dravet syndrome and Lennox-Gastaut Syndrome are now
nearing completion and will provide the placebo-controlled efficacy
and safety profile that patients and physicians have been calling
for. We look forward to these results in 2016."
Treatment effect data analysis used in this publication mainly
focused on monthly seizure frequency calculated over the entire
12-week treatment period (including a 4-week dose titration period)
compared to monthly seizure frequency during a 4-week baseline
observation period. This calculation is similar to the approach
being utilized in calculating the U.S. Food and Drug
Administration's (FDA) recommended primary efficacy endpoint in
GW's Epidiolex Phase 3 pivotal trials, which compare percent change
in the monthly seizure frequency over the entire 14-week treatment
period (including a 2-week dose titration period) to monthly
seizure frequency during the 4-week baseline observation
period.
Highlights from the publication of particular relevance to GW's
pivotal trials program in Dravet syndrome and LGS include:
- Dravet syndrome: The median reduction in monthly motor (i.e.,
convulsive) seizures was 49.8% (n=32). 50% of Dravet syndrome
patients had a 50% or greater reduction in monthly motor seizures.
During the last 4 weeks of therapy, 13% (n=4) were free of motor
seizures; these patients were also free of all other seizure types.
In Dravet syndrome patients who experienced them at baseline, there
was a median 69.2% reduction in monthly tonic seizures (n=6), 46.7%
reduction in monthly tonic-clonic seizures (n=29), and 83.3%
reduction in non-motor focal seizures (n=10).
- LGS: A median 68.8% reduction in average monthly atonic
seizures was observed (n=14). During the last 4 weeks of therapy,
21% (n=3) were free of atonic seizures and 3% (n=1) were totally
seizure free. In LGS patients who experienced motor and tonic
seizures at baseline, there were median 36.8% (n=30) and 44% (n=21)
reductions, respectively.
- Adverse events occurred in 79% of all patients treated with
cannabidiol (n=162). Adverse events reported in greater than 10% of
patients were somnolence (25%), decreased appetite (19%), diarrhea
(19%), fatigue (13%) and convulsion (11%). Most adverse events were
mild or moderate and transient. Five patients (3%) discontinued
treatment due to an adverse event.
- Serious adverse events were reported in 48 patients (30%),
including one death, regarded as unrelated to CBD. Serious adverse
events which were deemed possibly related to CBD occurred in 20
patients.
GW Pivotal Trials Program
GW is conducting two Phase 3 trials in Dravet syndrome and two
Phase 3 trials in LGS. GW also expects to commence Phase 3 clinical
development of Epidiolex in Tuberous Sclerosis Complex (TSC) in
early 2016.
For Dravet syndrome, GW expects to report top-line results from
the Phase 2/3 pivotal safety and efficacy study in the first
quarter of 2016 and results from the second Phase 3 trial around
mid-2016. The primary measure of efficacy in both trials will be
the comparison between Epidiolex and placebo in the percentage
change in number of monthly convulsive seizures (reported
tonic-clonic, tonic, clonic and atonic seizures) during the 14 week
treatment period compared with the 4 week baseline observation
period.
For LGS, GW expects to report top-line results from both Phase 3
trials in the second quarter of 2016. The primary measure of
efficacy in both trials will be the comparison between Epidiolex
and placebo in the percentage change in number of monthly drop
seizures (the sum of all reported atonic, tonic and tonic-clonic
seizures that were also deemed drop seizures (involving the entire
body, trunk or head that led or could have led to a fall, injury,
slumping in a chair or hitting the patient's head on a surface)
during the 14 week treatment period compared with the 4 week
baseline observation period.
The use of either "mean" or "median" analyses is determined
during a blinded analysis of the data - the mean is employed if the
data are parametric and the median is employed if the data are
non-parametric (which is the case for the expanded access program
and has historically been the case in many pediatric epilepsy
trials).
Reference:
1. Devinsky et al., Cannabidiol in Patients with Treatment
Resistant Epilepsy: an open-label interventional trial, Lancet
Neurology December 23, 2015
2. Devinsky et al, Epidiolex (Cannabidiol) in Treatment
Resistant Epilepsy, American Epilepsy Society Annual Meeting,
Poster, December 7, 2015
Note Regarding Expanded Access Studies
The expanded access studies we currently support are
uncontrolled, carried out by individual investigators independent
from us, and not typically conducted in strict compliance with Good
Clinical Practices, all of which can lead to a treatment effect
which may differ from that in placebo-controlled trials. These
studies provide only anecdotal evidence of efficacy for regulatory
review. These studies contain no control or comparator group for
reference and these patient data are not designed to be aggregated
or reported as study results. Moreover, data from such small
numbers of patients may be highly variable. Information obtained
from these studies, including the statistical principles that the
independent investigators have chosen to apply to the data, may not
reliably predict data collected via systematic evaluation of the
efficacy in company-sponsored clinical trials or evaluated via
other statistical principles that may be applied in those trials.
Reliance on such information to design our clinical trials may lead
to Phase 2 and 3 trials that are not adequately designed to
demonstrate efficacy and could delay or prevent our ability to seek
approval of Epidiolex. Expanded access programs provide supportive
safety information for regulatory review. Physicians conducting
these studies may use Epidiolex in
(MORE TO FOLLOW) Dow Jones Newswires
December 24, 2015 07:00 ET (12:00 GMT)
Gw Pharmaceuticals (LSE:GWP)
Historical Stock Chart
From Jun 2024 to Jul 2024
Gw Pharmaceuticals (LSE:GWP)
Historical Stock Chart
From Jul 2023 to Jul 2024