- LGS is one of the most challenging developmental and epileptic encephalopathies to manage because of high seizure frequency and significant neurodevelopmental impairment.
- More LGS study patients treated with FINTEPLA (fenfluramine) showed improvement in each of the BRIEF 2 indexes that have been used to assess behavior, emotion, and cognitive function in intractable epilepsy and other developmental conditions.
- Improvement was statistically significant for Cognition (27% vs 13% placebo, p=0.046) and the Global Executive Composite score (25% vs 11% placebo, p=0.034), where approximately twice as many patients achieved clinically meaningful improvement.
EMERYVILLE, Calif., April 22, 2021 (GLOBE NEWSWIRE) -- Zogenix (NASDAQ: ZGNX), a global biopharmaceutical company developing rare disease therapies, today announced new data showing the positive impact of treatment with FINTEPLA® (fenfluramine) oral solution on everyday executive function for children and young adults with Lennox-Gastaut syndrome (LGS). FINTEPLA is being investigated for the treatment of seizures associated with LGS, a rare, severe epilepsy that is one of the most challenging developmental and epileptic encephalopathies to manage due to the high seizure frequency and significant neurodevelopmental impairment patients experience.
The data, presented in an oral presentation and fireside chat at the virtual American Academy of Neurology (AAN) Annual Meeting this week, was the first presentation of FINTEPLA’s impact on LGS patients’ abilities to self-regulate behavior, emotions, and cognition. These new data complement earlier Phase 3 trial data demonstrating FINTEPLA’s ability to significantly reduce drop seizure frequency and, especially, generalized tonic-clonic seizure frequency (a primary risk factor for sudden unexpected death in epilepsy, or SUDEP) for many LGS patients.
"FINTEPLA-treated children and young adults with LGS showed improved overall self-regulation, with specific improvements in regulation of attention and cognition after 14 weeks in a Phase 3 double-blind randomized controlled trial,” said Kim Bishop, Ph.D. of Global Pharma Consultancy and lead author for the study. “Better self-regulation can have a positive impact on children's everyday functioning and reduce caregiver burden.”
Analysis
The objective of this post-hoc analysis was to assess the impact of FINTEPLA (fenfluramine) on everyday executive function as captured using the Behavior Rating Inventory of Executive Function (BRIEF®) as part of the Zogenix 14-week randomized Phase 3 clinical trial of children and young adults with LGS. The BRIEF assessments were completed by caregivers or parents as part of the trial, which included a total of 263 LGS patients aged 2-35 years. After a 4-week baseline, patients were randomized to placebo or one of two fenfluramine doses. Treatment continued for a combined 14-week titration and maintenance period. Age-appropriate versions of the BRIEF were administered at baseline and end of study.
This analysis included 137 patients (age 6-18) that had both baseline and end of-study BRIEF assessments (median age of 12 years), mapping the BRIEF ratings to the current BRIEF® 2 parent form, a shorter, 63-item version, which incorporates a large, 1,400-sample size normative population and statistics to support interpretation. This analysis did not include patients over 18 years of age because normative population data in adults is not yet available. The BRIEF 2 analysis utilizes the Reliable Change Index (RCI) for Behavior, Emotion, Cognition, and Global scores that represent a degree of confidence that the change represents a real effect (versus test-related errors and practice effects), and therefore is clinically meaningful. Associations between change in BRIEF 2 scores and combined active (0.2 and 0.7 mg/kg/day fenfluramine) versus placebo treatment groups were evaluated in cross tabulations using Somers’ D statistic.
Results
Mean age of patients in the FINTEPLA (n=92) vs. placebo (n=45) groups was 12 ± 3.6, with 44% of the FINTEPLA patients being female vs. 53% in the placebo group. The frequency of clinically elevated T-scores at baseline, defined as a T-score ≥65, was substantial, suggesting frequent impairment in executive function, as would be expected for children with LGS. Subjects with greater improvement in seizure control were more likely to show clinically meaningful improvements in executive functioning after the 14-week study duration.
More patients on FINTEPLA (fenfluramine) than placebo showed improvement in each of the four BRIEF 2 indexes (Behavior, Emotions, Cognition, and Global Executive Composite). Improvement was significantly greater for the CRI (Cognition) and GEC (Global Executive Composite) scores, indicating clinically meaningful improvement in the FINTEPLA (fenfluramine)-treated patients.
| Percentage of Patients Showing Clinically Meaningful Improvement (RCI ≥95% Certainty) in Active vs Placebo Treatment Groups | |||
| BRIEF® 2 Index | FINTEPLA® Fenfluramine (%) (N=92) | Placebo (%) (N=45) | P-Value |
| BRI (Behavior) | 24% | 13% | 0.118 |
| ERI (Emotions) | 19% | 16% | 0.665 |
| CRI (Cognition) | 27% | 13% | 0.046 |
| GEC (Global Executive Composite overarching summary score) | 25% | 11% | 0.034 |
“Analyses from our separate Phase 3 trials and long-term open label studies in Dravet syndrome, another difficult to treat rare epilepsy, showed that FINTEPLA provided sustained, clinically meaningful improvements in seizure control and executive function,” said Gail Farfel, Ph.D., Executive Vice President and Chief Development Officer at Zogenix and one of the study authors. “With a growing set of differentiating data in Lennox-Gastaut syndrome, we remain eager to continue advancing FINTEPLA as a potential new treatment option for patients living with this incredibly refractory disease.”
Presentation
Dr. Kim Bishop presented and discussed the data during Virtual AAN 2021; the slides from her presentation are archived on the Zogenix Newsroom.
About Lennox-Gastaut Syndrome
Lennox-Gastaut Syndrome (LGS) is a rare and devastating lifelong childhood-onset epilepsy that can arise from multiple different causes. LGS is characterized by many different seizure types, including many that result in frequent falls and injuries and that often don't respond to currently available seizure medications The intellectual and behavioral problems associated with LGS, as well as around-the-clock care requirements, add to the complexity of life with this disease.
About Zogenix
Zogenix is a global biopharmaceutical company committed to developing and commercializing therapies with the potential to transform the lives of patients and their families living with rare diseases. The company’s first rare disease therapy, FINTEPLA® (fenfluramine) oral solution, has been approved by the U.S. FDA and the European Medicines Agency and is in development in Japan for the treatment of seizures associated with Dravet syndrome, a rare, severe lifelong epilepsy. The company has two additional late-stage development programs, one in a rare epilepsy called Lennox-Gastaut syndrome and one in a mitochondrial disease called TK2 deficiency. Zogenix plans to initiate a study of FINTEPLA in a genetic epilepsy called CDKL5 Deficiency Disorder (CDD) and is also collaborating with Tevard Biosciences to identify and develop potential next-generation gene therapies for Dravet syndrome and other genetic epilepsies.
Forward-Looking Statement
Zogenix cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “indicates,” “will,” “intends,” “potential,” “suggests,” “assuming,” “designed,” and similar expressions are intended to identify forward-looking statements. These statements are based on Zogenix’s current beliefs and expectations. The inclusion of forward-looking statements should not be regarded as a representation by Zogenix that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risks and uncertainties inherent in patient outcomes and other risks described in Zogenix’s prior press releases as well as in public periodic filings with the U.S. Securities & Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Zogenix undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
CONTACTS:
Zogenix
Melinda Baker
Senior Director, Corporate Communications
+1 (510) 788-8732 | corpcomms@zogenix.com
Investors
Brian Ritchie
Managing Director, LifeSci Advisors LLC
+1 (212) 915-2578 | britchie@lifesciadvisors.com
Media
Stefanie Tuck, Vice President, Porter Novelli
+1 (978) 390-1394 | stefanie.tuck@porternovelli.com