ZYN002 successfully met the primary endpoint and
showed clinically meaningful improvements
Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), a clinical-stage
specialty pharmaceutical company dedicated to developing and
commercializing innovative pharmaceutically-produced transdermal
cannabinoid treatments, today announced positive top line results
from an open label exploratory Phase 2 FAB-C (Treatment of
Fragile X Syndrome
Anxiety and
Behavioral Challenges with
CBD)
clinical trial evaluating ZYN002 cannabidiol (CBD) gel in pediatric
and adolescent patients with Fragile X syndrome (FXS). The study
successfully met its primary endpoint, achieving a 46% improvement
(p<0.0001) in the total score of Anxiety, Depression, and Mood
Scale (ADAMS) at week twelve compared to baseline. ZYN002 also
achieved clinically meaningful improvements in all measures of the
Aberrant Behavior Checklist for Fragile X (ABC-FXS), which address
the key symptoms of FXS including social avoidance, temper
tantrums, repetitive movements, and hyperactivity.
“The data from the FAB-C trial are very exciting and demonstrate
that ZYN002 may have a profound effect on improving many of the
most disabling symptoms of Fragile X, such as anxiety and difficult
behaviors,” said Steven Siegel, MD, PhD Professor and Chair,
Psychiatry and Behavior Sciences, Keck School of Medicine of USC.
“Fragile X is a challenging genetic autism spectrum disorder, with
complex symptomatology that significantly impacts patients and
their families. Many children with Fragile X and their families
struggle with the lack of approved drugs to safely treat their
symptoms. This study suggests that ZYN002 is ready for the next
phase of development, and I believe that this drug holds great
promise as a potential treatment for these very difficult-to-treat
symptoms.”
With these data, Zynerba anticipates that it will
meet with the U.S. Food and Drug Administration (FDA) in the first
half of 2018 with the goal of moving quickly into a pivotal Phase
2/3 program in pediatric and adolescent patients with FXS in 2018.
The FDA has granted Zynerba Orphan Drug designation for the use of
CBD as treatment of patients with FXS. Orphan Drug designation is
granted to novel drugs that treat a rare disease or condition
affecting fewer than 200,000 patients in the U.S., and provides
benefits including a seven-year period of U.S. marketing
exclusivity upon marketing approval for the designated indication
and may provide a rapid path to market authorization.
“We are thrilled with the positive clinical results
of ZYN002 in the FAB-C trial; it is a major step forward for the
hundreds of thousands of patients worldwide with Fragile X who
currently have no approved therapeutic options to treat their
symptoms,” said Armando Anido, Chairman and Chief Executive Officer
of Zynerba. “The clinically meaningful improvements in Fragile X
symptoms and the excellent tolerability seen in the FAB-C trial are
compelling. These data will allow us to discuss the pathway to
approval in a meeting with the FDA, which we expect to take place
during the first half of 2018. I want to thank the patients,
families, physicians, study coordinators, and the Zynerba team for
their support of this important study.”
“The symptoms of Fragile X can be overwhelming to a
patient and caregiver, so I’m very enthusiastic about the responses
to ZYN002 that we saw during this study,” said Honey Heussler,
FRACP, Associate Professor at Children’s Health Queensland, Medical
Director Child Development and lead investigator in the FAB-C
study. “These data are extremely promising, particularly the
improvements in anxiety, social avoidance, and irritability as
measured by scales including ADAMS, ABC-FXS, and PARS-R.
Tolerability is essential in these patients, so I’m very pleased to
see that ZYN002 was well tolerated in Fragile X patients.”
Study DesignTwenty patients (3:1
males) aged 6 to 17 years of age (mean = 10.7) with Fragile X as
confirmed by molecular documentation of FMR1 full mutation were
enrolled in the open label FAB-C study. ZYN002 was added on to
other medications being administered. The first six weeks of the
study were designed to titrate dosing in patients. Dosing was
initiated at 50 mg daily and could be increased to 250 mg daily.
Weeks 7 through 12 of the study was a maintenance period where
patients were treated at the dose established at week six. At the
completion of the study, patients could enter an open label
extension study for up to 12 months.
Top-line data: Primary endpointThe
primary endpoint for the trial was the change in the total score of
the Anxiety, Depression, and Mood Scale (ADAMS) from baseline to
week 12. The ADAMS is a 28-item scale designed to assess general
anxiety, social avoidance, compulsive behavior, manic/hyperactive
behavior, and depressed mood. It has been validated in patients
with FXS.
Results for the primary endpoint are summarized as
follows:
|
Baseline |
|
Week 12 |
|
Change in Score |
|
% improvement |
|
p Value |
ADAMS: Total Score |
33.4 |
|
18.1 |
|
-14.1 |
|
45.81 |
% |
|
<0.0001 |
The subscales of ADAMS are as follows:
|
Baseline |
|
Week 12 |
|
Change in Score |
|
% Improvement |
|
p Value |
ADAMS: General
Anxiety Subscale |
10.0 |
|
4.6 |
|
-4.8 |
|
54.00 |
% |
|
<0.0001 |
|
|
|
|
|
|
|
|
|
|
ADAMS: Social
Avoidance Subscale |
10.2 |
|
4.8 |
|
-5.1 |
|
52.94 |
% |
|
0.0002 |
|
|
|
|
|
|
|
|
|
|
ADAMS: Compulsive
Behavior Subscale |
2.8 |
|
1.4 |
|
-1.2 |
|
50.00 |
% |
|
0.0262 |
|
|
|
|
|
|
|
|
|
|
ADAMS: Manic /
Hyperactive Behavior Subscale |
9.4 |
|
6.1 |
|
-2.7 |
|
35.11 |
% |
|
0.0003 |
|
|
|
|
|
|
|
|
|
|
ADAMS: Depressed Mood
Subscale |
2.8 |
|
2.0 |
|
-0.9 |
|
28.57 |
% |
|
0.1417 |
Top-line data: Secondary endpointsThe Company
evaluated multiple secondary endpoints including the Aberrant
Behavior Checklist – FXS Specific (ABC-FXS), a Clinical Global
Impression of Improvement (CGI-I), the Pediatric Anxiety Rating
Scale (PARS-R), Visual Analog Scales for Anxiety, Hyperactivity and
Tantrum/Mood Lability, the Vineland Adaptive Behavior III, a
Quality of Sleep measurement and the Pediatric Quality of Life
(PedsQL™). The results of the secondary endpoints reinforce the
results demonstrated in the ADAMS.
Results from the ABC-FXS are summarized as follows:
|
Baseline |
|
Week 12 |
|
Change in Score |
|
% improvement |
|
p Value |
ABC: Irritability -
"Has Temper Tantrums" |
18.2 |
|
10.6 |
|
-7.1 |
|
41.76 |
% |
|
0.0096 |
|
|
|
|
|
|
|
|
|
|
ABC: Hyperactivity -
"Disrupts Group Activities" |
14.5 |
|
9.7 |
|
-4.1 |
|
33.10 |
% |
|
0.0194 |
|
|
|
|
|
|
|
|
|
|
ABC: Socially
Unresponsive/Lethargic - "Does Not Pay Attention" |
8.7 |
|
4.1 |
|
-5.1 |
|
52.87 |
% |
|
0.0034 |
|
|
|
|
|
|
|
|
|
|
ABC: Social Avoidance -
"Seeks Isolation" |
5.1 |
|
2.3 |
|
-2.8 |
|
54.90 |
% |
|
0.0005 |
|
|
|
|
|
|
|
|
|
|
ABC: Stereotypy -
"Repetitive Movements" |
7.9 |
|
3.2 |
|
-4.9 |
|
59.49 |
% |
|
0.0006 |
|
|
|
|
|
|
|
|
|
|
ABC: Inappropriate
Speech - "Repeats Words or Phrases" |
6.1 |
|
3.5 |
|
-2.4 |
|
42.62 |
% |
|
0.0018 |
Safety dataZYN002 was shown to be very well
tolerated, and the safety profile was consistent with previously
released data from clinical trials. Two patients discontinued due
to worsening of pre-existing eczema. Four other patients
experienced an adverse event. No adverse events were considered
severe. No patient experienced drug-related GI events during the
12-week treatment period, and no THC was detected in the plasma.
Thirteen of the 18 patients who completed the study have enrolled
in the open label extension.
Conference call
informationZynerba management will host a live
conference call and webcast today at 8:30 am Eastern Time to
discuss the results of this clinical trial. The call can be
accessed by dialing (866) 573-0180 (U.S. and Canada) or (430)
775-1345 (international) and referencing conference ID 90858811. 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 Fragile X syndrome Fragile X syndrome is
an autism spectrum disorder affecting 1 in 4,000 males and 1 in
8,000 females. It is the most common inherited intellectual
disability in males and a significant cause of intellectual
disability in females. It is caused by a mutation in the Fragile X
Mental Retardation gene located on the X chromosome and leads to
dysregulation of the endocannabinoid pathway including the
reduction in endogenous cannabinoids (2-AG and anandamide). The
disorder negatively affects synaptic function, plasticity and
neuronal connections, and results in a spectrum of intellectual
disabilities, social anxiety and memory problems. In the US,
there are about 71,000 patients suffering with FXS.
About Our TechnologyCannabinoids are a class of
chemical compounds found in the Cannabis plant. The two primary
cannabinoids contained in Cannabis are cannabidiol, or CBD, and
∆9-tetrahydrocannabinol, or THC. Clinical and preclinical data
support the potential for CBD in treating epilepsy, arthritis and
Fragile X Syndrome, and THC has positive effects on treating pain.
Zynerba is developing therapeutic medicines that utilize innovative
transdermal technologies that, if successful, may allow for
sustained and controlled delivery of therapeutic levels of CBD and
THC. Transdermal delivery of cannabinoids may have benefits over
oral dosing because it allows the drug to be absorbed through the
skin directly into the bloodstream. This avoids first-pass liver
metabolism, potentially enabling lower dosage levels of active
pharmaceutical ingredients with a higher bioavailability and
improved safety profile. Transdermal delivery also avoids the
gastrointestinal tract, lessening the opportunity for GI related
adverse events and the potential degradation of CBD by gastric acid
into THC, which may be associated with unwanted psychoactive
effects. Using an established chemical pharmaceutical process for
manufacturing, Zynerba replicates the CBD and THC found in the
Cannabis plant. We believe that this will allow us to meet
stringent global regulatory agencies’ standards while ensuring that
we can efficiently supply the amount of product required to meet
the demand of the large markets that we are targeting.
About ZYN002Zynerba’s ZYN002 CBD gel is the
first and only pharmaceutically-produced CBD formulated as a
patent-protected permeation-enhanced gel and is being studied in
children with Fragile X Syndrome, osteoarthritis and in adult
epilepsy patients with focal seizures. ZYN002 is a clear,
permeation-enhanced gel that is designed to provide controlled drug
delivery transdermally with once- or twice-daily dosing.
About Zynerba Pharmaceuticals, Inc. Zynerba
Pharmaceuticals (NASDAQ:ZYNE) is dedicated to improving the lives
of people with severe health conditions where there is a high unmet
medical need by developing and commercializing
pharmaceutically-produced transdermal cannabinoid medicines
designed to meet the rigorous efficacy and safety standards
established by global regulatory agencies. Through the discovery
and development of these life-changing medicines, Zynerba seeks to
improve the lives of patients battling severe, chronic health
conditions including epilepsy, Fragile X syndrome, osteoarthritis,
fibromyalgia and peripheral neuropathic pain. Learn more at
www.zynerba.com and follow the Company 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 ZYN002 or ZYN001 from the U.S.
Food and Drug Administration (FDA) or foreign regulatory
authorities; even if ZYN002 or ZYN001 are approved, the Company may
not be able to obtain the label claims that it is seeking from the
FDA. In addition, the Company’s cash and cash equivalents may not
be sufficient to support its operating plan for as long as
anticipated. 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 success, cost and timing of
the Company’s product development activities, studies and clinical
trials; the success of competing products that are or become
available; 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 ContactsJim Fickenscher, CFO and VP
Corporate Development484.581.7483fickenscherj@zynerba.com
Will Roberts, VP Investor Relations and Corporate
Communications484.581.7489robertsw@zynerba.com
Media contactTheresa Dolge Tonic Life
CommunicationsOffice: 215-928-2748Theresa.Dolge@toniclc.com
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