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Zynerba Pharmaceuticals Announces Positive Top Line Results in ZYN002 Open Label Phase 2 FAB-C Study in Children with Fragile X Syndrome
ZYN002 successfully met the primary endpoint and showed clinically meaningful improvements
Zynerba to host conference call and webcast today,
“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
With these data, Zynerba anticipates that it will meet with the
“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
“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
Twenty 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 endpoint
The primary endpoint for the trial was the change in the total score of the Anxiety, Depression, and Mood Scale (
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
|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 endpoints
The 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|
ZYN002 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 information
Zynerba 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
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 Technology
Cannabinoids 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.
Zynerba’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.
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. For example, there can be no guarantee that the Company will obtain approval for ZYN002 or ZYN001 from the