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Zogenix, Inc.

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Zogenix’s Phase 3 program for Dravet syndrome continues to enroll patients in the U.S. and internationally, and the Company expects the availability of Phase 3 top-line data in Dravet syndrome in the second quarter of 2017, and potential regulatory submissions for approval to occur by year-end 2017. ZX008 is designated as an orphan drug in both the U.S. and Europe, and also received Fast Track designation in the U.S., for the treatment of Dravet syndrome.
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Source: press release, 12/05/16. http://ir.zogenix.com/phoenix.zhtml?c=220862&p=irol-newsArticle&ID=22274...

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Stephen J. Farr, Ph.D., President and CEO, commented on the ZX008 phase-III program. He stated, "As I stated earlier, the phase-III program is now commenced. With Study 1501, the first safety and efficacy trial underway in United States and the multinational trial which we call Study 1502 expected to begin in Europe in the coming weeks. I'll let Gail to provide you with an update on where we stand with the phase-III program shortly."
Source: Q4 2015 earnings conference call, 3/10/16.

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Zogenix Announces FDA Acceptance of Investigational New Drug Application for ZX008 Phase 3 Clinical Trial in Dravet Syndrome

SAN DIEGO, Dec. 14, 2015 (GLOBE NEWSWIRE) -- Zogenix, Inc. (Nasdaq:ZGNX), a pharmaceutical company developing therapies for the treatment of central nervous system (CNS) disorders, today announced that the U.S. Food and Drug Administration (FDA) has accepted the Company’s investigational new drug (IND) application for Zogenix’s lead product candidate, ZX008, as an adjunctive treatment of seizures in children with Dravet syndrome. The active IND now allows the Company to initiate its planned Phase 3 program for ZX008.

“We are pleased to have reached agreement with the FDA to proceed into Phase 3 clinical development, and are now focused on initiating the U.S.-based pivotal clinical trial for ZX008 prior to year-end, which would position us well to generate top-line results in 2016,” said Stephen J. Farr, Ph.D., President and CEO. “This is a significant milestone for Zogenix, as we believe ZX008 has the potential to provide Dravet patients and their families with an important treatment option for this catastrophic form of intractable epilepsy that begins in infancy.”

The Phase 3 program for ZX008 will consist of two randomized, double-blind placebo-controlled studies that will include two dose levels of ZX008 (0.2 mg/kg/day and 0.8 mg/kg/day, up to a maximum daily dose of 30 mg), as well as placebo. Zogenix intends to enroll 105 subjects in each of the two studies, with 35 patients in each treatment arm. One study will be conducted primarily in the U.S. and Canada, and the other will be a multi-national study, conducted primarily in Europe. The primary endpoint will be the change in frequency of convulsive seizures as compared to placebo. The key secondary endpoints include 40% and 50% responder analyses and convulsive seizure-free interval.
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Source: press release, 12/14/15. http://ir.zogenix.com/phoenix.zhtml?c=220862&p=irol-newsArticle&ID=21222...

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Zogenix Announces New Efficacy and Safety Data on ZX008 for Treatment of Seizures in Dravet Syndrome
New Clinical Data Presented at 69th Annual American Epilepsy Society Meeting on the Use of Low-Dose Fenfluramine in Managing Seizures Associated With Dravet Syndrome
SAN DIEGO, Dec. 7, 2015 (GLOBE NEWSWIRE) -- Zogenix, Inc. (Nasdaq:ZGNX), a pharmaceutical company developing therapies for the treatment of central nervous system (CNS) disorders, today announced new data demonstrating sustained effectiveness and cardiovascular-related safety for patients treated with ZX008 (low-dose fenfluramine) as an adjunctive therapy for seizures associated with Dravet syndrome. The data were presented at the 69th Annual American Epilepsy Society Meeting, taking place this week in Philadelphia, PA (see study data here and here). Zogenix expects to initiate a Phase 3 program for ZX008 in 2015. ZX008 is designated as an orphan drug in both the United States and Europe for the treatment of seizures associated with Dravet syndrome.

"In this new cohort of patients, we continue to achieve meaningful seizure control in Dravet syndrome patients using low-dose fenfluramine as adjunctive treatment," said Professor Berten Ceulemans, from the University of Antwerp, Belgium, and one of the authors of the poster regarding the study. "The most recent data corroborate both the effectiveness and the safety observations demonstrated in the original cohort of patients, which were published in 2012. We look forward to the start of Zogenix's ZX008 Phase 3 program evaluating low-dose fenfluramine as a potential adjunctive treatment for seizures associated with Dravet syndrome."

"The improvement in seizures and cardiovascular-related safety data from this ongoing open-label study continues to be quite compelling," said Bradley Galer, M.D., Chief Medical Officer of Zogenix. "These data further support ZX008's potential as a safe and effective adjunct treatment for uncontrolled seizures associated with Dravet syndrome. Dravet syndrome patients and their families remain in need of viable treatment alternatives for this devastating condition that causes frequent, severe and potentially life-threatening seizures that are often unresponsive to standard anti-epileptic medications. As such, we remain focused on advancing our preparations for the start of our Phase 3 program for ZX008, which we expect to initiate in 2015."

The data presented highlight the initial results from a new cohort of 7 Dravet syndrome patients who began add-on treatment with low-dose fenfluramine (5 mg to 15 mg per day) at various starting points between 2010 and 2014. Median treatment duration was 0.9 years (range 0.2 to 3.9 years). During the 90-day run-in period prior to initiating low-dose fenfluramine treatment, the median frequency of tonic-clonic seizures was 3.0 per month (range 0.4 to 39.7). At the 6-month evaluation after starting low-dose fenfluramine treatment, the median frequency of tonic-clonic seizures was 1.2 per month, and the median decrease was 73% (range 48-100%). Over the entire observation period, the median frequency of tonic-clonic seizures was 0.9 per month, and the median decrease was 84% (range 55-100%).

A separate poster reported that during this observation period from 2010 to 2015, treatment with low-dose fenfluramine was generally well-tolerated, and in this new cohort of patients, treatment for periods of 0.9 to 3.9 years did not result in any echocardiographic or clinical signs of cardiac valve abnormalities, pulmonary hypertension or any other cardiovascular abnormalities. The most common treatment-related adverse events were mild-to-moderate somnolence (n=6) and anorexia (n=4). There were no fenfluramine discontinuations due to adverse events or lack of effect.

The observed effectiveness, tolerability and cardiovascular-related safety with add-on, low-dose fenfluramine in this new cohort of Dravet syndrome patients extends the findings previously reported in the original cohort in 2012¹.

In addition, a separate, recently published study (see study data here) evaluated the mechanism of action for fenfluramine as a treatment for Dravet syndrome using a gene knockout zebrafish model. As a result of this study, certain 5-HTsubtype receptors that appear to be involved in the mechanism-of-action of fenfluramine were identified. Specifically, the elevation of serotonin levels and interaction with three 5-HT receptor subtypes, 5-HT1D, 5-HT2A and 5-HT2C, were found to be responsible for reducing both abnormal motor behavior and brain activity in this model of Dravet syndrome.
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Source: press release, 12/07/15. http://ir.zogenix.com/phoenix.zhtml?c=220862&p=irol-newsArticle&ID=21205...

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Zogenix Provides Regulatory Update for ZX008

Company Continues to Expect Phase 3 Clinical Program to Begin in Fourth Quarter of 2015

SAN DIEGO, Oct. 19, 2015 (GLOBE NEWSWIRE) -- Zogenix, Inc. (Nasdaq:ZGNX), a pharmaceutical company developing therapies for the treatment of central nervous system (CNS) disorders, today announced the recent receipt of a request from the U.S. Food and Drug Administration (FDA) for additional information related to the Company's proposed Phase 3 program for ZX008 prior to the FDA declaring Zogenix's Investigational New Drug Application (IND) effective. Zogenix has responded with the requested information required to initiate the clinical program. ZX008 previously received orphan drug designation from the FDA, and is expected to enter Phase 3 clinical studies during the fourth quarter of 2015 for the treatment of Dravet syndrome, a rare and debilitating form of epilepsy that begins in infancy.

The FDA's specific information requests are related to normative ranges for echocardiograms being conducted during the course of the pediatric Phase 3 program, and an amended Phase 3 study protocol to reflect a required follow-up echocardiogram 3 to 6 months after patients discontinue treatment with ZX008.

"We are confident that we have adequately addressed the FDA's information requests and look forward to receiving their response shortly," said Stephen Farr, Ph.D., President and CEO of Zogenix. "Importantly, our expected ZX008 clinical development timeline remains unchanged, including the expectation that the Phase 3 program will begin in the fourth quarter of 2015. We will provide further regulatory updates as appropriate."
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Source: press release, 10/19/15. http://ir.zogenix.com/phoenix.zhtml?c=220862&p=irol-newsArticle&ID=20983...

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Zogenix Announces New Efficacy Data From a Long-Term Study of Low-Dose Fenfluramine for Treatment of Dravet Syndrome

New data presented at European Paediatric Neurology Society Congress in Vienna, Austria includes 10 patients who continued treatment with low-dose fenfluramine for Dravet syndrome following the original study published in 2012, plus 2 new patients who began treatment in 2011

During 5-year follow-up period from 2010-2014:

At least 80% of patients experienced a greater than or equal to 75% reduction in seizure frequency every year
A majority of patients experienced long periods of seizure freedom
The drug was well tolerated and no patient discontinued treatment due to adverse events

SAN DIEGO, May 27, 2015 (GLOBE NEWSWIRE) -- Zogenix, Inc. (Nasdaq:ZGNX), a pharmaceutical company developing and commercializing unique therapies for the treatment of central nervous system (CNS) disorders, today announced new data demonstrating sustained efficacy and tolerability for patients treated with low-dose fenfluramine as an adjunctive therapy for Dravet syndrome. The data was authored by world-renown experts in the field of Dravet syndrome, Berten Ceulemans, M.D., Ph.D. and Lieven Lagae, M.D., Ph.D., from the Universities of Antwerp and Leuven in Belgium, and was presented at the European Paediatric Neurology Society meeting taking place this week in Vienna, Austria (see study data here). Zogenix intends to initiate Phase 3 clinical studies for ZX008, the Company's investigational proprietary pediatric formulation of low-dose fenfluramine, during the second half of 2015. ZX008 is designated as an orphan drug in both the U.S. and Europe for the treatment of Dravet syndrome.

Data table - http://ir.zogenix.com/phoenix.zhtml?c=220862&p=irol-newsArticle&ID=20535...

Patients with Dravet syndrome experience frequent, severe and potentially life-threatening seizures that typically start in the first year of life. These seizures do not respond to standard anti-epileptic medications and current treatment options are very limited.

"The most important element of treating patients with Dravet syndrome is to reduce the frequency of all seizures and to prevent status epilepticus, which is a continuous state of seizure," said Prof. Berten Ceulemans. "As this most recent data analysis demonstrates, in our experience, we have been able to achieve major seizure control for Dravet syndrome patients using a low-dosage form of fenfluramine as adjunctive therapy. It is my hope that these outcomes will be replicated in the Phase 3 program to be undertaken by Zogenix."

"We continue to be encouraged by the results of the ongoing open-label study of the use of low-dose fenfluramine in patients with Dravet syndrome. It is very exciting to observe a reduction of greater than or equal to 75% in seizure frequency for at least 80% of patients over the latest 5-year follow-up period with the use of fenfluramine as an add-on treatment. In addition, there continues to be a majority of Dravet patients who experience sustained periods of seizure-freedom. We believe these data represent the most robust, long-term data set of any investigational treatment for Dravet syndrome, especially since some of these patients have been treated for well over 20 years," said Stephen Farr, Ph.D., Chief Executive Officer of Zogenix. Farr continued, "Our current focus is to finalize the Phase 3 study protocol, based on recent feedback received from the U.S. Food and Drug Administration, and initiate the studies of ZX008 in the U.S. and Europe."

The results presented are from the latest 5-year follow-up period (2010-2014) in a group of Dravet syndrome patients being treated with low-dose fenfluramine (10 mg to 20 mg per day). This analysis, which includes ten patients from the original study group (as published in 20121) and two patients who began treatment in 2011, demonstrated that during any given year of the follow-up period, at least 80% of patients achieved a greater than or equal to 75% reduction in the frequency of seizures. In addition, three patients (25%) were seizure-free for all 5 years and five patients (42%) were seizure-free for 2 to 4 years. The use of low-dose fenfluramine in this group of patients was shown to be generally well tolerated, with the most common adverse events being transient loss of appetite and fatigue/somnolence. No clinically meaningful cardiac adverse events were noted. No patient discontinued treatment due to adverse events.

In addition, a recently published translational research study2 to elucidate fenfluramine's mechanism of action in Dravet syndrome demonstrated the ability of fenfluramine to significantly reduce locomotion and eliminate epileptiform EEG activity in a gene knockdown zebrafish model of Dravet syndrome. These data support the clinical results obtained in the Belgium cohort of patients.
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Source: press release, 5/27/15. http://ir.zogenix.com/phoenix.zhtml?c=220862&p=irol-newsArticle&ID=20535...

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Study 1501 - A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Trial of Two Fixed Doses of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy in Children and Young Adults With Dravet Syndrome
Estimated Enrollment: 130
Study Start Date: January 2016
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
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Source: clinical trials.gov. https://clinicaltrials.gov/ct2/show/NCT02682927?term=zx008&rank=1

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Compound/DeviceSpecialtyIndicationCompound ClassTarget
ZX008 (low dose Fenfluramine)NeurologyDravet syndrome5-HT2B receptor agonist5-HT2B receptor

Mechanism of action: ZX008 (low dose Fenfluramine) is a 5-HT2B receptor agonist and 5-HT reuptake inhibitor.

Phase of Development: III

Event Type: Data: Phase III trial results

Dates: 2017-04-01 - 2017-06-30

Results: Pending