Zogenix Announces New Positive Data for Its Investigational Drug FINTEPLA® in Dravet Syndrome

EMERYVILLE, Calif., Oct. 25, 2019 (GLOBE NEWSWIRE) -- Zogenix, Inc. (NASDAQ: ZGNX), a global pharmaceutical company developing rare disease therapies, today announced positive new data for its investigational drug, FINTEPLA® (ZX008, fenfluramine), for the treatment of seizures associated with Dravet syndrome. The data were presented in five scientific posters, available here, at the recent Childhood Neurology Society (CNS) Congress. The posters include data showing long-term, clinically meaningful reduction in convulsive seizure frequency in young Dravet syndrome patients (under 6 years of age) in an ongoing Open-Label Extension (OLE) study, as well as data from a post-hoc analysis showing clinically meaningful and profound reduction in the frequency of high-risk tonic-clonic (grand-mal) seizures in Dravet syndrome patients treated in two previously completed Phase 3 clinical trials. Other data include the results of a Phase 1 study to assess the potential drug-drug interaction of fenfluramine and cannabidiol (CBD).

“These data continue to demonstrate the significant clinical impact Fintepla has shown in studies of Dravet syndrome patients,” said Bradley Galer, M.D., Executive Vice President and Chief Medical Officer at Zogenix. “These new results clearly show the impact this drug candidate has had on some of the most vulnerable patients, those who are younger than 6 years of age, as well as those suffering from generalized tonic-clonic seizures, a recognized risk factor for sudden unexplained death in epilepsy (SUDEP).”

Below are summaries of the data presented at the 2019 CNS Annual Meeting:

• ZX008 (Fenfluramine HCl Oral Solution) Provides Long-Term, Clinically Meaningful Reduction of Convulsive Seizure Frequency in Young (<6 years old) Dravet Syndrome Subjects: Analysis from Long-Term Open-Label Study (J. Sullivan, R. Nabbout, K. Knupp et al)

  This analysis explored the safety and effectiveness of fenfluramine by age group in Zogenix’s ongoing OLE study of FINTEPLA (Study 1503). A total of 42 of 158 (26.6%) subjects enrolled in the OLE trial were under 6 years of age. The median baseline monthly convulsive seizure frequency for this age group prior to treatment was 10.7 seizures per month (ranging from 4.0 to 147.3).

  At the time of analysis, the median decrease in monthly convulsive seizure frequency for the under 6 years of age group over the entire observation period compared to baseline was 75.5% (p<0.001). This compared to a median decrease of 60.1% (p<0.001) in the older, over-6 years of age group and a median decrease of 63.6% (p<0.001) in the overall study population (aged 2-18 years). Fenfluramine was generally well-tolerated and no case of valvular heart disease or pulmonary arterial hypertension was observed in any patient at any time.
  

• ZX008 Fenfluramine HCl Significantly Reduces Frequency of Generalized Tonic-Clonic Seizures in Dravet Syndrome: Pooled Analysis from Two Phase 3 Clinical Trials (O. Devinsky, J. H. Cross, A. Gil-Nagel et al.)

  Dravet syndrome patients commonly experience generalized tonic-clonic seizures, which are often treatment resistant and have been identified as a major risk factor for SUDEP. This pooled analysis of two randomized, placebo-controlled Phase 3 studies (Study 1 & Study 1504) evaluated the impact of FINTEPLA on generalized tonic-clonic (grand mal) seizures, and focal-to-bilateral tonic-clonic seizures. A total of 206 enrolled patients were randomized to placebo (n=84), or to treatment with FINTEPLA 0.7 (n=40), 0.4 (n=43), or 0.2 (n=39) mg/kg/day.

  The median baseline monthly frequency of generalized tonic-clonic seizures ranged from 8.0 to 12.3 per month in the four dose groups, and decreased by 80%, 64%, and 48% in the FINTEPLA 0.7, 0.4, and 0.2 mg/kg/day groups, respectively, compared to 10% in the placebo group. Focal-to-bilateral tonic-clonic seizures were experienced by fewer patients and had a median baseline frequency of 2.0 to 4.7 per month. During treatment, median percent reductions in focal-to-bilateral tonic-clonic seizure frequency were 97%, 33% and 69% in the FINTEPLA 0.7, 0.4, and 0.2 mg/kg/day groups, respectively, and 39% in the placebo group. Fenfluramine was generally well-tolerated and no case of valvular heart disease or pulmonary arterial hypertension occurred in any patient. The most common treatment emergent adverse events occurring in ≥10% of patients in any treatment group were decreased appetite, lethargy, fatigue, somnolence, and diarrhea.

• A Phase 1, Single-Dose, Open-Label Pharmacokinetic Study to Investigate the Drug-Drug Interaction Potential of ZX008 (Fenfluramine HCl Oral Solution) and Cannabidiol (B. Boyd, S. Smith, G. Farfel et al)

  This poster described data from a Phase 1, single-dose, open-label study to assess the tolerability and pharmacokinetic profiles (potential drug-drug interaction) of fenfluramine with and without co-administration of CBD. The results of the study showed that the effects of CBD on fenfluramine are unlikely to require dose adjustments when the drugs are co-administered.

• Relationships Between Self-Regulation and Quality of Life: Results from a Phase 3 Study of ZX008 (Fenfluramine HCl Oral Solution) in Children and Young Adults with Dravet Syndrome (K. Bishop, G. Gioia, P. Isquith, G. Morrison)

  This study evaluated the relationship between caregiver-reported executive control functions and quality of life (QOL) ratings in children and young adults with Dravet syndrome being treated in Zogenix’s Study 1504. Caregivers completed the Pediatric Quality of Life Inventory^™ (PedsQL^™) 4.0 Generic Core Scales and the Behavior Rating Inventory for Executive Function^® (BRIEF^®) instruments at baseline and again at the end of the study.

  The results demonstrated that increasing the FINTEPLA dose was associated with greater improvements in executive control, which caregivers correlated to improved QOL in most domains, including physical, social, school, psychosocial and total summary scores. We believe that the apparent dose-response effect observed could suggest an important contribution of seizure control or drug effect on executive function in Dravet syndrome patients.

• Defining a Minimal Clinically Important Difference in Seizure Frequency Using Data from a Phase 3 Clinical Study of Add-On, Low-Dose ZX008 (Fenfluramine HCl Oral Solution) in Dravet Syndrome Patients Receiving an Antiepileptic Drug Regimen Containing Stiripentol (A. Gammaitoni, J. Sullivan, D. Dlugos et al)

  An antiepileptic drug (AED) is conventionally considered to have clinically meaningful efficacy if patients in the study population show a ≥50% reduction in seizure frequency, but this threshold is largely derived from observation without formal hypothesis testing in a controlled clinical trial setting. This presentation used an analysis of Study 1504 to define a clinically meaningful change in monthly convulsive seizure frequency versus baseline and found that a threshold of ≥37.5% reduction in seizure frequency was best associated with a rating of “Much Improved” or “Very Much Improved” on both investigator and caregiver Clinical Global Impression of Improvement assessments. Because this threshold is lower than the 50% accepted improvement used by regulators, further studies of additional AED combinations are needed to identify other factors that could impact caregiver and investigator ratings.

About FINTEPLA® (ZX008, fenfluramine oral solution) Studies
International Phase 3 studies of FINTEPLA (ZX008, fenfluramine) were double-blind, randomized, placebo-controlled studies with 12-week treatment periods, in which ZX008 or placebo was added to current regimens of antiepileptic drug. The studies measured the change in frequency of convulsive seizures before and during treatment. Studies 1501 and Study1502 in Dravet syndrome included patients not taking stiripentol; Study 1504 included patients whose treatment regimen did include stiripentol. (Study 1 was an analysis of the first 120 patients in studies 1501 and 1502.) Study 1503 is an ongoing international, open-label extension study of patients who have successfully completed treatment in studies 1501 and 1502.

In all studies, FINTEPLA was well-tolerated and demonstrated rapid and clinically meaningful reductions in convulsive seizures at all test doses. The most common adverse events were decreased appetite, diarrhea, fatigue, lethargy, pyrexia, and nasopharyngitis. Incidence of serious AEs was comparable across placebo and FINTEPLA treatment groups. No development of valvular heart disease or pulmonary hypertension was observed in any patient.

About Zogenix
Zogenix is a global pharmaceutical company committed to developing and commercializing transformative therapies that improve the lives of patients and their families living with serious rare diseases. The Company has two late-stage drug candidates: FINTEPLA® (ZX008, fenfluramine) for the treatment of seizures associated with Dravet and Lennox-Gastaut syndrome, two rare and often-catastrophic childhood-onset epilepsies, and MT1621, an investigational deoxynucleoside substrate enhancement therapy for the treatment of Thymidine Kinase 2 deficiency (TK2d), an inherited mitochondrial DNA depletion disorder. Zogenix’s NDA for FINTEPLA in Dravet syndrome has been resubmitted to the FDA and an MAA for the same indication is under review by the European Medicines Agency. FINTEPLA is also in development in Japan. The Company anticipates top-line data for FINTEPLA in Lennox-Gastaut syndrome in the first quarter of 2020.

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 include: the potential for FINTEPLA, if approved, to provide an important new treatment option for patients and families living with Dravet syndrome; and the potential timing of top-line data the on-going Phase 3 trial of FINTEPLA in patients with Lennox-Gastaut syndrome (LGS). 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 Zogenix’s business, including, without limitation: the FDA may disagree that the existing safety and efficacy data is sufficient to approve the NDA; the FDA may require Zogenix to conduct the additional chronic toxicity studies noted in the Refusal to File letter, dated April 3, 2019, or other studies or information in connection with its review of the NDA; the timing of the data from Study 1601 of FINTEPLA in patients suffering from LGS could be delayed; the results of Study 1601 may differ from the results of prior clinical studies in LGS or may demonstrate adverse safety data compared to the prior Phase 3 clinical trials of FINTEPLA; the FDA may not agree with Zogenix’s interpretation of the results of the clinical trials of FINTEPLA; later developments with the FDA that may be inconsistent with feedback received at prior meetings with the FDA; additional data from Zogenix’s ongoing studies may contradict or undermine the data submitted in the NDA for FINTEPLA; the uncertainties associated with the clinical development and regulatory approval of product candidates such as FINTEPLA; unexpected adverse side effects or inadequate therapeutic efficacy of FINTEPLA that could limit approval and/or commercialization, or that could result in recalls or product liability claims; 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
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