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Zynerba Pharmaceuticals Announces Positive Top Line Data from BELIEVE 1 Open Label Phase 2 Study of Zygel™ in Developmental and Epileptic Encephalopathies (DEE)
- Study Achieves a 44% Median Seizure Reduction in Focal Impaired Awareness (Complex Partial) and Convulsive Seizures in DEE Patients by Month Two; Reductions were Sustained through Month Six of Treatment with Zygel -
- At Least 42% of these Patients Experienced a ≥50% Improvement from Month Two through Month Six -
- Qualitative Assessments Demonstrate Improvements in Seizure Intensity and Duration, and
Socio-behavioral and Cognitive Impairments -
“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
“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
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
|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.
|Median % reduction in seizure frequency||18%||6%||46%||23%||63%||51%|
|≥50% responder rate||36%||36%||46%||40%||64%||60%|
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.
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 Zygel from the
Source: Zynerba Pharmaceuticals, Inc.