LONDON and CARLSBAD, California, January 24, 2018 /PRNewswire/ --
- First
well-controlled clinical study of cannabidiol in Lennox-Gastaut
syndrome, a rare, severe, form of childhood-onset epilepsy that is
difficult to treat -
- Pharmaceutical
formulation of cannabidiol significantly
reduced drop seizure frequency
in patients with poor seizure control
despite the use of multiple anti-epileptic
drugs -
GW Pharmaceuticals plc (Nasdaq: GWPH, "GW," "the Company" or
"the Group"), a biopharmaceutical company focused on discovering,
developing and commercializing novel therapeutics from its
proprietary cannabinoid product platform, along with its U.S.
subsidiary Greenwich Biosciences, announced today
that The Lancet has published results
from a Phase 3 study of Epidiolex® (cannabidiol) in
patients with Lennox-Gastaut syndrome
(LGS).[1] Epidiolex, GW's lead product candidate
and the potential first in a new category of anti-epileptic drugs
(AEDs), is a pharmaceutical formulation of purified cannabidiol
(CBD), a cannabinoid lacking euphoric side effects, which is being
studied for the treatment of a number of rare, severe
pediatric-onset epilepsy disorders. In this study, Epidiolex
significantly reduced monthly drop seizure frequency compared to
placebo in highly treatment-resistant patients when added to
existing treatment. Treatment with Epidiolex was generally well
tolerated, with a safety profile consistent with prior reported
experience.
A New Drug Application (NDA) submission to the U.S. Food and
Drug Administration (FDA) for Epidiolex in the treatment of LGS and
Dravet syndrome (another rare childhood-onset epilepsy) was
accepted in December with an assigned PDUFA goal date of
June 27th 2018 and,
if approved, the medicine is expected to be available in the U.S.
by prescription in the second half of 2018. A Marketing
Authorisation Application (MAA) was submitted to the European
Medicines Agency (EMA) in December
2017, with an expected decision in early 2019.
"Publication of this landmark study by The
Lancet is an exciting achievement and marks the second
time that Epidiolex data have been published in a highly
prestigious journal, following last year's publication
in The New England Journal of Medicine," said
Justin Gover, GW's Chief Executive
Officer. "These publications highlight the potential of Epidiolex
to address the significant unmet need in LGS and Dravet syndrome,
two very challenging epilepsy conditions, and we look forward to
working with the FDA and EMA as they review our marketing
applications for Epidiolex. We are absolutely focused on the goal
of making this important potential new therapy available to
appropriate patients and their caregivers as quickly as
possible."
LGS is a rare, lifelong form of epilepsy that begins in
childhood and is associated with a high mortality
rate[2] and significant developmental
delays.[3],[4] LGS patients suffer from multiple
types of seizures, including drop seizures which can result in
falls and other injuries. Results from this study represent the
only well-controlled clinical evaluation of a cannabinoid
medication for this severe, drug-resistant condition.
"The publication of these positive results is an exciting
milestone for the LGS community and we are encouraged that a new
treatment option could soon be available," said Christina SanInocencio, executive director of
the Lennox-Gastaut Syndrome Foundation. "Additional treatment
options are desperately needed for patients who continue to
struggle with uncontrolled seizures and these results offer much
needed hope to those living with this debilitating condition."
"LGS is one of the most difficult types of epilepsy to treat and
the majority of patients do not have an adequate response to
existing therapies," said Elizabeth
Thiele, MD, PhD, director of pediatric epilepsy at
Massachusetts General Hospital, professor of Neurology at
Harvard Medical School and lead author
of the study publication. "These results show that Epidiolex
may provide clinically meaningful benefits for patients with
LGS."
The study randomized 171 patients (86 to CBD; 85 to placebo)
ages two to 55 years (average age 15), with LGS whose seizures were
not controlled by their current AED regimen, to receive either
cannabidiol (20mg/kg/day) or placebo in addition to existing
treatment. Conducted in 24 study centers in the United States and Europe, on average, patients were taking
approximately three AEDs, having previously tried and discontinued
an average of six other AEDs. At baseline, patients had a median
frequency of 74 drop seizures per month (drop seizures were defined
as atonic, tonic or tonic-clonic 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).
Over the 14-week treatment period (two-week dose escalation
period followed by 12 weeks of maintenance), patients taking
cannabidiol had a significantly greater median reduction in drop
seizures compared to placebo (44 percent vs. 22 percent; p=0.0135),
the study's primary endpoint. Sensitivity analyses confirmed that
the treatment effect of CBD was established during the first month
of treatment and was sustained over the entire treatment
period.
Results from key secondary endpoints showed that significantly
more patients on cannabidiol experienced a 50 percent or greater
reduction in drop seizures compared to placebo (44 percent vs. 24
percent; p=0.0043) and total seizure frequency was significantly
reduced with cannabidiol compared to placebo (median percent
reduction of 41 percent vs. 14 percent; p=0.0005). CBD
patients/caregivers were significantly more likely to report an
improvement in overall condition with cannabidiol than placebo (58
percent vs. 34 percent; OR 2.54, 95% CI 1.5-4; p=0.0012) based on
the Subject/Caregiver Global Impression of Change (S/CGIC)
scale.
Cannabidiol was generally well tolerated in the trial. The
most common adverse events (AEs) (>10 percent) were diarrhea,
somnolence, pyrexia, decreased appetite and vomiting. Overall, 86
percent of patients taking Epidiolex and 69 percent of patients
taking placebo experienced an AE, and most were mild or moderate.
Of those patients who experienced AEs, the events resolved by the
end of the trial for 61 percent of cannabidiol patients and 64
percent of placebo patients.
Twenty patients on cannabidiol experienced serious AEs,
including one fatal case of acute respiratory distress syndrome
(considered unrelated by the Investigator), compared with four
patients with serious AEs on placebo. Twelve patients taking
cannabidiol discontinued treatment due to AEs compared with one
patient taking placebo.
Across the cannabidiol development program, the most common
reported adverse reactions are somnolence, decreased appetite,
diarrhoea, pyrexia, fatigue, lethargy, rash, nasopharyngitis, and
pneumonia; dose-related reversible elevation of liver transaminases
without elevation of bilirubin were also observed.
"Uncontrolled seizures significantly impact the lives of
patients and their families and there is a tremendous need for new
options in difficult-to-treat epilepsies such as LGS," said
Philip Gattone, president and CEO,
Epilepsy Foundation. "This randomized, controlled clinical study
provides positive evidence of the potential role of cannabidiol in
reducing seizures and we are excited about the possibility of
a new treatment option for LGS."
About Lennox-Gastaut Syndrome
The onset of LGS typically occurs between ages of 3 to 5 years
and can be caused by a number of conditions, including brain
malformations, severe head injuries, central nervous system
infections, and genetic neuro-degenerative or metabolic conditions.
In up to 30 percent of patients, no cause can be found. Patients
with LGS commonly have multiple seizure types including drop and
convulsive seizures, which frequently lead to falls and injuries,
and non-convulsive seizures. Resistance to anti-epileptic drugs
(AEDs) is common in patients with LGS. Most children with LGS
experience some degree of intellectual impairment, as well as
developmental delays and aberrant behaviors.
About Dravet Syndrome
Dravet syndrome is a severe infantile-onset and highly
treatment-resistant epileptic encephalopathy frequently associated
with genetic mutations in the SCN1A sodium channels. Onset of
Dravet syndrome occurs typically during the first year of life in
previously healthy and developmentally normal infants. Initial
seizures are often body temperature related, severe, and
long-lasting. Over time, patients with Dravet syndrome often
develop multiple types of seizures, including tonic-clonic,
myoclonic, and atypical absences and are prone to bouts of
prolonged seizures including status epilepticus, which can be life
threatening. Risk of premature death including SUDEP (sudden
unexpected death in epilepsy) is elevated in patients with Dravet
syndrome. Additionally, the majority will develop moderate to
severe intellectual and development disabilities and require
lifelong supervision and care. There are currently
no FDA-approved treatments and nearly all patients continue to
experience seizures and other medical needs throughout their
lifetime.
About
Epidiolex® (cannabidiol)
Epidiolex, GW's lead cannabinoid product candidate is a
pharmaceutical formulation of purified cannabidiol (CBD), which is
in development for the treatment of several rare childhood-onset
epilepsy disorders. GW has submitted a New Drug Application with
the FDA for Epidiolex as adjunctive treatment for seizures
associated with LGS and Dravet syndrome, which has been assigned a
goal date of 27 June 2018 and, if
approved, the medicine is expected to be available by prescription
in the second half of 2018. GW has also submitted a Marketing
Authorisation Application (MAA) to the European Medicines Agency
(EMA) in December 2017 with an
expected decision date in early 2019. To date, GW has received
Orphan Drug Designation from the FDA for Epidiolex for the
treatment of Dravet syndrome, LGS, TSC and IS. Additionally, GW has
received Fast Track Designation from the FDA for the treatment of
Dravet syndrome and conditional grant of rare pediatric disease
designation by FDA. The Company has also received Orphan
Designation from the European Medicines Agency, or EMA, for
Epidiolex for the treatment of LGS, Dravet syndrome, West syndrome
and TSC. GW is currently evaluating additional clinical development
programs in other orphan seizure disorders including Phase 3 trials
in Tuberous Sclerosis Complex and Infantile Spasms.
About GW Pharmaceuticals plc and Greenwich
Biosciences
Founded in 1998, GW is a biopharmaceutical company focused on
discovering, developing and commercializing novel therapeutics from
its proprietary cannabinoid product platform in a broad range of
disease areas. GW, along with its U.S. subsidiary Greenwich
Biosciences, is advancing an orphan drug program in the field of
childhood epilepsy with a focus on Epidiolex (cannabidiol), for
which GW has submitted an NDA to the FDA for the adjunctive
treatment of LGS and Dravet syndrome. The Company continues to
evaluate Epidiolex in additional epilepsy conditions and currently
has ongoing clinical trials in Tuberous Sclerosis Complex and
Infantile Spasms. GW commercialized the world's first plant-derived
cannabinoid prescription drug,
Sativex® (nabiximols), which is approved for the
treatment of spasticity due to multiple sclerosis in numerous
countries outside the United
States. The Company has a deep pipeline of additional
cannabinoid product candidates which includes compounds in Phase 1
and 2 trials for gliobastoma, schizophrenia and epilepsy. For
further information, please visit http://www.gwpharm.com.
Forward-looking statements
This news release contains forward-looking statements that
reflect GW's current expectations regarding future events,
including statements regarding financial performance, the timing of
clinical trials, the timing and outcomes of regulatory or
intellectual property decisions, the relevance of GW products
commercially available and in development, the clinical benefits of
Epidiolex® (cannabidiol) and the safety profile and
commercial potential of Epidiolex. Forward-looking statements
involve risks and uncertainties. Actual events could differ
materially from those projected herein and depend on a number of
factors, including (inter alia), the success of GW's research
strategies, the applicability of the discoveries made therein, the
successful and timely completion and uncertainties related to the
regulatory process, and the acceptance of Sativex, Epidiolex and
other products by consumer and medical professionals. A further
list and description of risks and uncertainties associated with an
investment in GW can be found in GW's filings with the U.S.
Securities and Exchange Commission, including the most recent Form
20-F filed on 4 December 2017.
Existing and prospective investors are cautioned not to place undue
reliance on these forward-looking statements, which speak only as
of the date hereof. GW undertakes no obligation to update or revise
the information contained in this press release, whether as a
result of new information, future events or circumstances or
otherwise.
References:
- Thiele EA, Marsh ED, French JA, et al. Cannabidiol (CBD)
Significantly Reduces Drop Seizure Frequency in Lennox-Gastaut
Syndrome (LGS): Results of a Multi-center, Randomized,
Double-blind, Placebo-controlled Trial (GWPCARE4). Lancet 2017;
376;2011-20.
- Autry AR, Trevathan E, Van Naarden Braun K, Yeargin-Allsopp M.
Increased risk of death among children with Lennox-Gastaut syndrome
and infantile spasms. J Child Neurol. 2010;25(4):441-447.
- LGS Foundation. About Lennox-Gastaut Syndrome. Available
at http://www.lgsfoundation.org/aboutlgs . Accessed
October 23, 2017.
- National Institute of Health. Lennox-Gastaut syndrome.
Available
at https://ghr.nlm.nih.gov/condition/lennox-gastaut-syndrome#definition .
Accessed October 23, 2017.
Enquiries:
GW Pharmaceuticals plc
Stephen Schultz, VP Investor
Relations
(U.S.) +1-917-280-2424 / +1-401-500-6570
U.S. Media Enquiries:
Sam Brown Inc. Healthcare
Communications
Christy Curran +1-615-414-8668
Mike Beyer, +1-312-961-2502
EU Media Enquiries:
FTI Consulting
Con Franklin, +44(0)7817-573-659