Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in
innovative pharmaceutically-produced transdermal cannabinoid
therapies for rare and near-rare neuropsychiatric disorders, today
announced the Company has received guidance from the U.S. Food and
Drug Administration (FDA) on a confirmatory Phase 3 trial of Zygel
in patients with Fragile X syndrome (FXS). The trial, which will be
called RECONNECT (A
Randomiz
ed,
Double-Blind, Pla
cebo-C
ontrolled,
Multiple-Ce
nt
er,
Effi
cacy and Safe
ty Study of
ZYN002 Administered as a Transdermal Gel to Children and
Adolescents with Fragile X Syndrome), is designed to evaluate the
efficacy and safety of Zygel in children and adolescents with FXS.
The study is planned to confirm the positive results observed in a
population of responders in the Company’s CONNECT-FX trial, a
randomized, double-blind, placebo-controlled trial that assessed
the efficacy and safety of Zygel as a treatment for the behavioral
symptoms of FXS previously conducted by the Company. The Company
believes that the results, if positive, from RECONNECT will be
sufficient to support the submission of a New Drug Application for
Zygel in patients with FXS.
“Following productive discussions and alignment with the FDA, we
believe we have a clear path forward for Zygel in Fragile X
syndrome. We are excited to advance Zygel into the RECONNECT trial,
a pivotal, multi-national, confirmatory Phase 3 trial in patients
with FXS in the third quarter of 2021,” said Armando Anido,
Chairman and Chief Executive Officer of Zynerba. “If the results
are positive, Zygel could become the first FDA approved treatment
option for the significant unmet medical need that affects patients
with FXS and their families.”
The RECONNECT trial will be an 18-week trial which will enroll
approximately 200 children and adolescents of which approximately
160 patients will have complete (100%) methylation of their FMR1
gene and approximately 40 patients will have partial methylation of
their FMR1 gene. The primary endpoint for the trial will be the
change in the Aberrant Behavior Checklist-Community FXS Specific
(ABC-CFXS) Social Avoidance subscale in patients who have complete
methylation of their FMR1 gene. All patients, including the cohort
of partially methylated patients, will be included in a key
secondary endpoint analysis.
Complete Methylation Results from
CONNECT-FX
The Company performed an analysis of the CONNECT-FX population
within those patients having complete methylation of their FMR1
gene (n = 137 of 212 in the intent to treat population) to evaluate
the effect of Zygel versus placebo. One patient did not have a
post-baseline efficacy measure and was therefore not included in
the efficacy analysis.
Baseline demographics for patients with complete methylation of
the FMR1 gene are shown below. The group is similar to the
previously reported full data set of patients and the cohort of
patients with ≥90% methylation. The majority of patients were male
and the children had a mean age of 9 to 10 years old.
|
Placebo |
Zygel |
Total |
n |
65 |
72 |
137 |
Age (years) |
9.7 |
9.5 |
9.6 |
Sex – Males |
|
|
|
n |
43 |
47 |
90 |
% |
66% |
65% |
66% |
Weight – kg: |
|
|
|
Median |
34.5 |
35.7 |
35.2 |
Range – Min, Max |
16.8, 104.7 |
18.6, 87.0 |
16.8, 104.7 |
Baseline psychoactive medications, % |
69% |
56% |
62% |
The results in the cohort of patients with complete methylation
of the FMR1 gene across the primary and key secondary endpoints
that will be used in the RECONNECT trial are summarized below.
|
PlaceboN=64 |
ZygelN=72 |
|
|
|
Baseline Mean |
Week 12 Mean Change |
Baseline Mean |
Week
12MeanChange |
Treatment Difference** |
OddsRatio |
Treatment P-Value |
Primary Endpoint: |
|
|
|
|
|
|
|
ABC-CFXS Social Avoidance Subscale |
7.25 |
-1.84 |
6.88 |
-2.92 |
-1.08 |
|
0.027* |
Secondary Endpoints: |
|
|
|
|
|
|
|
ABC-CFXS Irritability Subscale |
27.84 |
-3.98 |
28.89 |
-5.83 |
-1.85 |
|
0.220 |
CGI-I at Week 12 (Any Improvement) |
– |
36% |
– |
50% |
|
1.75 |
0.128 |
*Statistically significant vs. placebo**A negative treatment
difference demonstrates that Zygel patients improved versus
placebo
“The treatment difference versus placebo and p value on the
primary endpoint of improvement in the ABC-CFXS Social Avoidance
subscale in patients with complete methylation are consistent with
the previously reported findings in patients with at least 90%
methylation, despite the fact that the study was not powered to
evaluate either of these patient populations.” said Dr. Joseph
Palumbo, Chief Medical Officer of Zynerba Pharmaceuticals, Inc. “We
believe the CONNECT-FX trial was instrumental in advancing our
understanding of the science of Fragile X Syndrome. We look forward
to leveraging what we learned as we seek to confirm our findings in
the RECONNECT trial.”
Conference call information
Zynerba management will host a live conference call and
webcast today at 5:30 pm Eastern Time to discuss the design of
the RECONNECT Trial. The call can be accessed by dialing (800)
708-4540 (U.S. and Canada) or (847) 619-6397 (international) and
referencing conference ID 50161974. To access the live webcast or
the replay, visit the investor page of the Company’s website
at http://ir.zynerba.com/. The webcast will be recorded and
available on the Company’s website for 30 days.
About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative
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.
About Fragile X Syndrome (FXS)
Fragile X syndrome is a rare genetic developmental disability
that is the leading known cause of both inherited intellectual
disability and autism spectrum disorder, affecting 1 in 3,600 to
4,000 males and 1 in 4,000 to 6,000 females. It is the most common
inherited intellectual disability in males and a significant cause
of intellectual disability in females, and the leading genetic
cause of autism spectrum disorder (ASD). The disorder negatively
affects synaptic function, plasticity and neuronal connections, and
results in a spectrum of intellectual disabilities and behavioral
symptoms, such as social avoidance and irritability. In the
US, there are about 71,000 people suffering with FXS, approximately
60% of whom have complete methylation of the FMR1 gene.
FXS is caused by a mutation in FMR1, a gene which modulates a
number of systems, including important effects on the
endocannabinoid system, and most critically, codes for a protein
called FMRP. This protein helps regulate the production of other
proteins and plays a role in the development of synapses,
which are critical for relaying nerve impulses, and in regulating
synaptic plasticity. The FMR1 mutation manifests as multiple
repeats of a DNA segment, known as the CGG triplet repeat. In most
neurotypical people, the FMR1 gene correctly codes for the FMRP
protein. In neurotypical individuals, there are CGG repeats, but
these repeats only occur between 5 and 40 times. As a result, FMRP
is manufactured at levels that enable control over behaviors like
social avoidance and anxiety. In people with full mutation of the
Fragile X gene, the CGG segment is repeated more than 200 times and
in most cases causes the FMR1 gene to not function. However, the
methylation of the FMR1 gene also plays a role in determining
functionality of the gene. For patients with complete (100%)
methylation, the FMR1 gene is silenced, therefore, no FMRP is
produced, and the systems and processes that are expected to be
affected by FMRP become dysregulated.
Cautionary Note on Forward-Looking
Statements
This 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. 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 expectations, projections and
estimates regarding expenses, future revenue, capital requirements,
incentive and other tax credit eligibility, collectability and
timing, and availability of and the need for additional financing;
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, including
the RECONNECT trial, 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; the Company’s planned
RECONNECT trial may not be determined to be sufficient to support
an NDA submission; actions or advice of the U.S. Food and Drug
Administration 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;
the Company’s expectations regarding its ability to obtain and
adequately maintain sufficient intellectual property protection for
its product candidates; the timing and outcome of current and
future legal proceedings; and the extent to which health epidemics
and other outbreaks of communicable diseases, including COVID-19,
could disrupt our operations or adversely affect our business and
financial conditions. 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 Contacts
Peter VozzoWestwicke/ICROffice: 443.213.0505Cell:
443.377.4767Peter.Vozzo@Westwicke.com
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