Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in
innovative pharmaceutically-produced transdermal cannabinoid
therapies for rare and near-rare neuropsychiatric disorders, today
announced positive top line results from the open label Phase 2
BELIEVE 1 (Open La
bel Study to Assess the Safety
and
Efficacy of Zygel™ (ZYN002) Administered as a
Transderma
l Gel to Ch
ildren and
Adol
escents with De
velopmental
and
Epileptic Encephalopathy) clinical trial. The
trial assessed the safety and efficacy of Zygel in developmental
and epileptic encephalopathies (DEE), a heterogeneous group of rare
pediatric epilepsy syndromes, including Dravet syndrome (DS) and
Lennox-Gastaut syndrome (LGS). DEE is characterized by the presence
of multiple focal and generalized seizure types and severe
cognitive and behavioral impairment. The most common and
debilitating seizure types in people with epilepsy are focal
impaired-awareness and convulsive seizures. Patients who
experienced these seizure types achieved 44% to 58% monthly median
reductions in seizures compared to baseline from month two to month
six of treatment with Zygel. Further, qualitative assessments by
caregivers in the study demonstrate that use of Zygel may result in
improved socio-behavioral and cognitive symptoms of DEE. Zygel was
also well tolerated in this study.
“The data from the BELIEVE 1 clinical trial are promising and
suggest that Zygel may reduce seizure frequency in many types of
difficult to treat developmental and epileptic encephalopathies and
improve important behavior deficits, alertness, social
interactions, and enable the child to be well enough to attend
school more consistently,” said Ingrid Scheffer, AO, MBBS, PhD,
FRACP, Professor and Chair, Paediatric Neurology Research, The
University of Melbourne, and an investigator in the BELIEVE 1
trial. “DEE are the most challenging and poorly controlled
epilepsy disorders with many symptoms that adversely affect patient
and family function. I believe that this drug holds promise as a
potential treatment for DEE.”
“We are encouraged by the positive top line results of the
BELIEVE 1 trial of Zygel in children and adolescents with DEE, and
we believe these data represent an important step forward for these
patients and their families,” said Armando Anido, Zynerba’s
Chairman and Chief Executive Officer. “These results suggest that
Zygel may produce clinically meaningful reductions in seizures and
may improve many of the difficult behaviors and symptoms, such as
seizure intensity, fatigue, social isolation, poor cognition, and
language deficits. Once we complete our analyses of the data, we
intend to seek a meeting with the FDA, likely in the first half of
next year, to discuss the clinical pathway to approval.”
Study Design
The six-month BELIEVE 1 clinical trial is an exploratory open
label multi-dose Phase 2 clinical trial designed to evaluate the
safety and efficacy of Zygel in children and adolescents (three to
<18 years) with DEE as classified by the International League
Against Epilepsy (ILAE) (Scheffer et al. 2017). Forty-eight
patients with confirmed DEE were enrolled in the clinical trial and
are included in the safety data for the trial. Forty-six patients
are included in the modified intent-to-treat population (mITT). The
two patients excluded from the intent-to-treat population included
one patient who did not complete 80% of their seizure diaries and a
second patient who did not complete a minimum of eighty days of
treatment. Enrolled patients received weight-based initial doses of
250 mg or 500 mg daily of Zygel. Patients could be titrated up to
1,000 mg daily.
Baseline Patient Demographics
The BELIEVE 1 trial enrolled 48 patients between the ages of
three and 16 (mean=10.5; median=10.0). Fifty-four percent of
patients were male, and 46% were female. Patients weighed between
14.3 and 110 kilograms (mean=39.3; median=36.1). Patient BMI ranged
between 12.5 and 35.4 (mean=19.2; median=18.6).
Top-line Efficacy Results
Of the 46 patients in the mITT population, 33 (72%) had focal
impaired-awareness seizures (FIAS; previously known as complex
partial seizures) and/or convulsive seizures (focal to bilateral
tonic-clonic seizures and generalized
tonic-clonic seizures) at baseline. These patients experienced
a mean baseline seizure count of 64 FIAS and/or convulsive
seizures, and a median baseline seizure count of 8.2 FIAS and/or
convulsive seizures. Compared to baseline seizure frequency, these
patients experienced a ≥44% median reduction in seizures from month
two onwards using monthly seizure frequency normalized to 28 days
(SF28).
Fifty-five percent (55%) of patients with FIAS and/or convulsive
seizures experienced a ≥50% median reduction in seizures at month
six of treatment with Zygel.
FIAS and convulsive seizures |
Month 1(n=33) |
Month 2(n=33) |
Month 3(n=33) |
Month 4(n=32) |
Month 5(n=32) |
Month 6(n=29) |
Median % reduction in seizure frequency |
16% |
44% |
44% |
47% |
58% |
51% |
≥50% responder rate |
30% |
42% |
46% |
47% |
63% |
55% |
Thirteen of the 46 patients had a variety of non-FIAS and
non-convulsive seizure types at baseline. The number of individual
seizure types in these patients was too small to draw definitive
conclusions and further analyses are warranted.
Patients with either DS or LGS who experienced FIAS and/or
convulsive seizures (n=11) experienced a 51% median reduction in
FIAS and/or convulsive seizures at month six of treatment compared
to baseline. Sixty percent (60%) of patients with DS or LGS
experienced a ≥50% median reduction in FIAS or convulsive seizures
at month six of treatment with Zygel.
Lennox-Gastaut and Dravet syndromes |
Month 1(n=11) |
Month 2(n=11) |
Month 3(n=11) |
Month 4(n=11) |
Month 5(n=11) |
Month 6(n=10) |
Median % reduction in seizure frequency |
18% |
6% |
46% |
23% |
63% |
51% |
≥50% responder rate |
36% |
36% |
46% |
40% |
64% |
60% |
Safety data
Zygel was well tolerated, and the safety profile was consistent
with previously released data from Zygel clinical trials. Eight
patients discontinued the study; one discontinued as a result of an
application site reaction, and seven discontinued as a result of
withdrawal of consent or perceived lack of efficacy. Through six
months of therapy, ninety-six percent (96%) of patients experienced
a treatment emergent adverse event (TEAE) and 60% of patients
experienced a treatment related adverse event. Most were mild to
moderate. The most common treatment related adverse events (in
>5% of patients) are application site dryness (8.3%),
application site pain (8.3%), and somnolence (8.3%). Ten patients
reported a serious adverse event (SAE); most were
infection-related. Two SAEs (lower respiratory tract infection and
status epilepticus) were determined to be possibly related to
treatment. There were no patient deaths during the study.
Qualitative analysis of the impact of Zygel on
behavioral and cognitive symptoms
Parents and caregivers were asked to provide a qualitative
assessment regarding their child’s overall experiences during
treatment with Zygel. The experiences of 43 patients are summarized
below.
- 58% reported improved vitality (e.g. alertness / awareness,
energy)
- 51% reported improvement in seizures
- 47% reported improved cognition and concentration
- 44% reported improved socially avoidant behaviors
- 28% reported that their child attended school on time / more
often
- 26% reported difficulty in application of the gel to their
child (e.g. time it takes for gel to dry)
About Developmental and Epileptic Encephalopathies
(DEE)DEE is a heterogeneous group of epilepsy syndromes
that may be associated with severe cognitive impairment and
behavioral disturbances. These disorders are often progressive, and
are highly resistant to treatment. DEE includes a number of rare
and ultra-rare epilepsy syndromes including early myoclonic
encephalopathy, epileptic encephalopathy with continuous spike and
wave during sleep, and certain syndromes including Ohtahara, West,
Landau-Kleffner, Lennox-Gastaut, Doose and Dravet. Improved seizure
control may have a positive impact on development and quality of
life.
About Zynerba Pharmaceuticals, Inc. Zynerba
Pharmaceuticals is the leader in pharmaceutically-produced
transdermal cannabinoid therapies for rare and near-rare
neuropsychiatric disorders. We are committed to improving the lives
of patients and their families living with severe, chronic health
conditions including Fragile X syndrome, autism spectrum disorder,
22q11.2 deletion syndrome, and a heterogeneous group of rare and
ultra-rare epilepsies known as developmental and epileptic
encephalopathies. Learn more at www.zynerba.com and follow us on
Twitter at @ZynerbaPharma.
Cautionary Note on Forward-Looking
StatementsThis press release contains forward-looking
statements within the meaning of The Private Securities Litigation
Reform Act of 1995. We may, in some cases, use terms such as
“predicts,” “believes,” “potential,” “proposed,” “continue,”
“estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,”
“could,” “might,” “will,” “should” or other words that convey
uncertainty of future events or outcomes to identify these
forward-looking statements. Such statements are subject to numerous
important factors, risks and uncertainties that may cause actual
events or results to differ materially from the Company’s current
expectations. For example, there can be no guarantee that the
Company will obtain approval for Zygel from the U.S. Food and Drug
Administration (FDA) or foreign regulatory authorities; even if
Zygel is approved, the Company may not be able to obtain the label
claims that it is seeking from the FDA. Management’s expectations
and, therefore, any forward-looking statements in this press
release could also be affected by risks and uncertainties relating
to a number of other factors, including the following: the
Company’s cash and cash equivalents may not be sufficient to
support its operating plan for as long as anticipated; the
Company’s ability to obtain additional funding to support its
clinical development programs; the results, cost and timing of the
Company’s clinical development programs, including any delays to
such clinical trials relating to enrollment or site initiation;
clinical results for the Company’s product candidates may not be
replicated or continue to occur in additional trials and may not
otherwise support further development in a specified indication or
at all; actions or advice of the FDA and foreign regulatory
agencies may affect the design, initiation, timing, continuation
and/or progress of clinical trials or result in the need for
additional clinical trials; the Company’s ability to obtain and
maintain regulatory approval for its product candidates, and the
labeling under any such approval; the Company’s reliance on third
parties to assist in conducting pre-clinical and clinical trials
for its product candidates; delays, interruptions or failures in
the manufacture and supply of the Company’s product candidates the
Company’s ability to commercialize its product candidates; the size
and growth potential of the markets for the Company’s product
candidates, and the Company’s ability to service those markets; the
Company’s ability to develop sales and marketing capabilities,
whether alone or with potential future collaborators; the rate and
degree of market acceptance of the Company’s product candidates;
and the Company’s expectations regarding its ability to obtain and
adequately maintain sufficient intellectual property protection for
its product candidates. This list is not exhaustive and these and
other risks are described in the Company’s periodic reports,
including the annual report on Form 10-K, quarterly reports on Form
10-Q and current reports on Form 8-K, filed with or furnished to
the Securities and Exchange Commission and available
at www.sec.gov. Any forward-looking statements that the
Company makes in this press release speak only as of the date of
this press release. The Company assumes no obligation to update
forward-looking statements whether as a result of new information,
future events or otherwise, after the date of this press
release.
Zynerba ContactWilliam Roberts, Vice President,
Investor Relations and Corporate CommunicationsZynerba
Pharmaceuticals484.581.7489 robertsw@zynerba.com
Media contactMolly DevlinEvoke
KYNE215.928.2199Molly.Devlin@evokegroup.com
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