JAMA Neurology Publishes Phase 3 Study of Zogenix Investigational Drug FINTEPLA® in Dravet Syndrome Patients Taking Stiripentol-Containing Antiepileptic Drug Regimens

• Addition of FINTEPLA to stiripentol-inclusive regimens provided a 54% greater reduction in study patients’ mean monthly convulsive seizure frequency compared to placebo
  
  
• A significantly greater proportion of study patients taking FINTEPLA compared to placebo experienced clinically meaningful (≥ 50%) or profound (≥ 75%) seizure reduction
  
  
• Patients in the FINTEPLA treatment group also experienced significantly longer periods of seizure freedom

EMERYVILLE, Calif., Dec. 02, 2019 (GLOBE NEWSWIRE) -- Zogenix, Inc. (NASDAQ: ZGNX), a global pharmaceutical company developing rare disease therapies, announced today that JAMA Neurology has published the results of Zogenix’s Phase 3 study (Study 1504) of the investigational drug, FINTEPLA^® (ZX008, fenfluramine oral solution), in Dravet syndrome patients whose antiepileptic drug treatment regimens included stiripentol but who were still experiencing a high number of convulsive seizures. Dravet syndrome is a rare, severe, and very difficult to treat infantile-onset epilepsy characterized by frequent, disabling seizures. The study demonstrated that adding FINTEPLA to these patients’ treatment regimens led to a significant and clinically meaningful (> 50%) reduction in monthly convulsive seizure frequency (MCSF).

“Because it is common for physicians to use stiripentol for their Dravet syndrome patients, it was important to evaluate the benefit and tolerability of adding FINTEPLA to a stiripentol-inclusive treatment regimen in those patients who were still experiencing frequent convulsive seizures,” said study author, Professor Rima Nabbout, M.D., Ph.D., Department of Pediatric Neurology, Reference Center for Rare Epilepsies, Necker Enfants Malades Hospital, Paris, France, and Principal Investigator of Study 1504. “We found that adding FINTEPLA to a regimen containing stiripentol resulted in a significant and clinically meaningful reduction in monthly convulsive seizure frequency early and for the duration of the study period. Patients in the FINTEPLA arm also experienced longer seizure-free intervals, which is important as many were previously experiencing multiple seizures per week.”

Study 1504 was an international, double-blind, placebo-controlled Phase 3 study of 87 Dravet syndrome patients age 2-19 taking background anti-epileptic drug regimens that included stiripentol, randomized to placebo (n=44) or FINTEPLA 0.4 mg/kg/day (n=43)*. The study was conducted at 28 centers in Canada, France, Germany, the Netherlands, Spain, the United Kingdom and the United States. Eligible patients in the trial were experiencing seizures that were poorly controlled with their current anti-seizure medications consisting of stiripentol plus clobazam and/or valproic acid. After a 6-week period to establish baseline seizure frequency, patients were randomized to receive FINETPLA starting at a dose of 0.2 mg/kg/day, twice-daily with gradual blinded titration over a 3 week period to 0.4 mg/kg/d (maximum of 17 mg per day)* over 3 weeks. Patients maintained their regimen for an additional 12 weeks at a stable dose, then either continued treatment in an open-label extension study or discontinued treatment.

The study met its primary efficacy endpoint and all key secondary endpoints. Patients treated with FINTEPLA achieved a 54% greater reduction in mean MCSF than those receiving the placebo (95% CI, 35.6%-67.2%; p<0.001). Additionally, 54% of patients treated with FINTEPLA experienced a clinically meaningful (>50%) reduction in MCSF versus 5% with placebo (p<0.001). Profound seizure reduction (>75% reduction in MCSF) was experienced by 35% of FINTEPLA-treated patients compared to 2% with placebo (p=0.003). The median longest seizure-free interval was 22 days (3.0-105.0) with FINTEPLA and 13 days (1.0-40.0) with placebo (p=0.004).

In the study, FINTEPLA was generally well-tolerated and demonstrated a safety profile consistent with the findings of Zogenix’s first Phase 3 study of FINTEPLA in Dravet syndrome, called Study 1, as well as with findings from an analysis of the company’s ongoing open-label extension study (Study 1503). The most common adverse events in Study 1504 were decreased appetite (19 patients taking fenfluramine [44%] vs 5 taking placebo [11%]), fatigue (11 [26%] vs 2 [5%]), diarrhea (10 [23%] vs 3 [7%]), and pyrexia (11 [26%] vs 4 [9%]). Across all three studies, no patient exhibited clinical or echocardiographic evidence of valvular heart disease or pulmonary arterial hypertension.

“Given the devastating and lifelong impacts associated with the frequent convulsive seizures experienced by Dravet syndrome patients, we are very much encouraged by the results of this study in patients still having many seizures on a stiripentol-containing medication regimen and by its publication in JAMA Neurology,” said Bradley S. Galer, M.D., Executive Vice President and Chief Medical Officer at Zogenix. “We hope that this and our other clinical study data will help clinicians better understand the potential that FINTEPLA, if approved, could have for patients needing additional novel treatment options.”

* Note: Zogenix originally presented Study 1504 data results in December 2018 at the 72^nd American Epilepsy Society (AES) Annual Meeting.  In that and other presentations, Zogenix expressed doses of FINTEPLA (ZX008, fenfluramine oral solution) as doses of the HCl salt, with an upper limit of 0.5 mg/kg/day and 20 mg maximum daily dose. Due to current regulatory guidelines, Zogenix has chosen to express study doses as the fenfluramine base-equivalent, with an upper limit dosing of 0.4 mg/kg/day and 17 mg maximum daily dose.

About Zogenix
Zogenix is a global pharmaceutical company committed to developing and commercializing transformative therapies to improve the lives of patients and their families living with rare diseases. The company has two late-stage development programs underway: FINTEPLA® (ZX008, fenfluramine oral solution) for the treatment of seizures associated with Dravet and Lennox-Gastaut syndromes, two rare and often-catastrophic childhood-onset epilepsies, and MT1621, a novel substrate enhancement therapy for the treatment of a rare genetic disorder called TK2 deficiency.  The company’s New Drug Application for FINTEPLA for Dravet syndrome has been accepted for review by the U.S. Food & Drug Administration; its application for FINTEPLA for Dravet syndrome is under review by the European Medicines Agency. Zogenix expects top-line data from its Phase 3 study of FINTEPLA in Lennox-Gastaut syndrome (LGS) in the first quarter of 2020. FINTEPLA is also in development in Japan.

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 benefits FINTEPLA may have, if approved; the impacts that Dravet syndrome has on patients; and the potential timing of top-line data for Study 1601. 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 of FINTEPLA for the treatment of Dravet syndrome; 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; top-line data the Company reports is based on preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data related to the clinical trial and such top-line data may not accurately reflect the complete results of a clinical trial, and the FDA may not agree with the Company’s interpretation of such results; 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 and MT1621; 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; risks associated with the acquisition of Modis and integration of Modis’ operations into Zogenix’s business, including an increase in near and long-term expenditures, exposure to unknown liabilities and diversion of Zogenix’s management’s time and attention; 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.

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