Positive Data from Second Pivotal Phase 3 Trial (Study 1504) Consistent with Results of First Phase 3 Trial in Showing Highly Significant Convulsive Seizure Reduction for FINTEPLA versus Placebo
Clinically Meaningful Reduction in Convulsive Seizure Frequency for FINTEPLA Maintained Over Phase 3 Open-Label Extension Trial (Study 1503)
Data Presented During Late-Breaker Session at 72nd
American Epilepsy Society Annual Meeting
Company to Host Investor Update Meeting Today, December 3, 2018
EMERYVILLE, Calif., Dec. 03, 2018 (GLOBE NEWSWIRE) -- Zogenix, Inc. (NASDAQ:ZGNX), a pharmaceutical company developing therapies for the treatment of rare diseases, announced today that late-breaking data will be presented on the use of its investigational drug, FINTEPLA® (ZX008; low-dose fenfluramine), in children and young adults with Dravet syndrome. These three presentations will include data from the second pivotal Phase 3 trial (Study 1504), and long-term efficacy and safety data from a formal interim analysis of the ongoing open-label extension (OLE) trial (Study 1503). A post-hoc exploration of the clinical meaningfulness of seizure control from the first pivotal Phase 3 trial (Study 1) will also be presented. The data will be presented at the 72nd American Epilepsy Society (AES) Annual Meeting in New Orleans. Full posters can be found on www.zogenix.com here.
Study 1504: Positive Results from a Second Phase 3 Clinical Trial
Results from Study 1504 (poster 3.461) will be presented as a follow-up to top-line results that were released in July 2018. Patients (n=87) in Study 1504 were taking a background anti-epileptic drug (AED) medication regimen that included stiripentol and were randomized to placebo (n=44) or FINTEPLA 0.5 mg/kg/day (n=43). Following a six-week baseline observation period, patients were titrated to their target dose over three weeks and then remained at that fixed dose for 12 weeks. Consistent with Study 1, Study 1504 met the primary endpoint and all key secondary endpoints. Results demonstrated the statistically significant efficacy of FINTEPLA when added to a stiripentol regimen in children and young adults with Dravet syndrome.
Clinically Meaningful Seizure Reduction
Children and young adults treated with FINTEPLA achieved a 54.0% greater reduction in mean monthly convulsive seizures compared to placebo (p<0.001). The median reduction in monthly convulsive seizure frequency was 63.1% in the FINTEPLA group compared to 1.1% in placebo patients.
The Study 1504 results showed the odds of achieving a clinically meaningful (≥50%) or substantial (≥75%) reduction in convulsive seizure frequency were 26 and 24 times higher, respectively, among patients treated with FINTEPLA 0.5 mg/kg/day than in patients treated with placebo. The study also demonstrated statistically significant differences in seizure-free intervals, with a median longest seizure-free interval of 22 days in patients treated with FINTEPLA 0.5 mg/kg/day vs.13 days for patients in the placebo group (p=0.004).
Safety Profile Consistent with Study 1; No Signal of Cardiovascular Toxicity
The incidence of serious adverse events was similar in both the treatment and placebo groups. The most common adverse events in the FINTEPLA group were decreased appetite (44%), pyrexia (26%), fatigue (26%), diarrhea (23%), and nasopharyngitis (16%).
There was no evidence of valvular heart disease (valvulopathy) or pulmonary hypertension in any patient at any time during the trial. These safety results are consistent with the findings of Study 1, as well as the now released interim analysis of long-term safety data from the OLE trial. Across all trials, no safety signal of any valvular heart disease has been identified to date.
Study 1503: Interim Analysis of Ongoing Open-Label Extension Trial Confirms Durability of Effectiveness and No Cardiac Toxicity for FINTEPLA in Dravet Syndrome
Data from Study 1503 will be presented in two posters, one that focuses on effectiveness and overall tolerability of FINTEPLA (poster 3.463) and a second on the long-term cardiovascular assessments and observations (poster 3.453).
A total of 232 patients in Study 1503 were included in the interim analysis of the ongoing OLE trial. The median duration of treatment with FINTEPLA was 256 days and the range was 58-634 days (equivalent to 161 patient-years of exposure to FINTEPLA). A total of 22 (9.5%) patients discontinued treatment: lack of efficacy (16), subject withdrawal (2), adverse event (1), Sudden Unexpected Death in Epilepsy (SUDEP) (1), physician decision (1), and withdrawal by caregiver (1). More than 90% of patients remained in the study.
Substantial Reduction in Seizure Frequency and Maintenance Over Time
The median percent reduction in monthly convulsive seizure frequency over the entire OLE treatment period was 66.8% (compared with baseline frequency established in the core Phase 3 studies). Over the same period, 64.4% of children and young adults demonstrated a >50% reduction in convulsive seizure frequency and 41.2% demonstrated a >75% reduction.
Reductions in convulsive seizure frequency was noted at the first timepoint measured, one month, and continued over the entire treatment period analyzed. Based on the most current assessment during the OLE treatment period, 66.1% of caregivers and 65.9% of investigators rated patients as “much improved” or “very much improved.”
“These long-term data show that the significant reductions in convulsive seizure frequency observed in children and young adults in the pivotal Phase 3 trials are maintained over extended periods of treatment with FINTEPLA,” said Joseph Sullivan, M.D., Director of the Pediatric Epilepsy Center at UCSF Benioff Children’s Hospital San Francisco. “These positive findings further confirm the potential of FINTEPLA to transform the treatment paradigm for people living with Dravet and their families.”
Long-Term Safety of FINTEPLA Assessed; No Signal of Cardiovascular Toxicity
The occurrence of adverse events was consistent with the Phase 3 placebo-controlled studies. The most common adverse events occurring in more than 10% of children and young adults were pyrexia (22%), nasopharyngitis (20%), decreased appetite (16%), influenza (12%), diarrhea (11%), and upper respiratory tract infection (10%). A total of 13.4% of children lost >7% body weight at some point during the trial; in 42% of those children weight loss abated during the period covered by the interim analysis. Over the course of the OLE treatment period, one patient died from SUDEP that was deemed unrelated to FINTEPLA.
A total of 703 color doppler echocardiograms were performed to assess cardiovascular health at baseline, week 4 or 6, and then every 3 months during the OLE trial. No patient developed valvular heart disease (valvulopathy) or pulmonary arterial hypertension at any time after daily treatment with FINTEPLA.
“Long-term safety results are a critical aspect of the profile for any investigational medicine,” said study author Dr. Wyman Lai, Co-Medical Director, CHOC Children's Heart Institute. “I believe these results provide strong support that the positive benefit-risk profile of FINTEPLA that was observed in both pivotal Phase 3 trials extends to its longer-term use in the ongoing open-label extension trial.”
“Based on the strength and consistency of our clinical data for FINTEPLA in Dravet syndrome, we expect to conclude the submission of a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) early in the first quarter of 2019,” said Gail Farfel, Ph.D., Executive Vice President and Chief Development Officer of Zogenix. “We are confident in the potential of FINTEPLA to positively impact the lives of patients and their families and are committed to advancing through the regulatory process as efficiently as possible.”
Investor Update Lunch at AES
Zogenix will host an Investor Update Lunch on FINTEPLA today, December 3, 2018, from 12:00 PM to 2:00 PM CST. If you are an institutional investor, sell-side analyst, investment banker, or business development professional, please RSVP in advance if you plan to attend, as space is limited. A live webcast and replay of the presentations will be accessible here.
Zogenix is committed to developing and commercializing transformative therapies to improve the lives of patients and their families living with rare diseases. For more information, visit www.zogenix.com.
Forward Looking Statements
Zogenix cautions you that statements included in this press release or in the poster presentations 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 Zogenix’s belief that Study 1504 are consistent with the results from Study 1; the results observed to date supporting the potential long-term safety and efficacy of FINTEPLA; the timing of submission of the NDA for FINTEPLA; and Zogenix’s belief that FINTEPLA may positively impact the lives of patients, if approved by the FDA. 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 or in any poster presentation due to the risks and uncertainties inherent in Zogenix's business, including, without limitation: the uncertainties associated with the clinical development and regulatory approval of product candidates such as FINTEPLA; the additional data presented is based on Zogenix’s analysis of the efficacy and safety data received to date, and such data may be supplemented as Zogenix receives additional data from the OLE study and such data may not accurately reflect the complete results of the study, and the FDA may not agree with Zogenix’s interpretation of such results; 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; the potential that the FDA will disagree Zogenix’s analysis of Study 1503, Study 1504 or Study 1, including the safety profile of FINTEPLA; the potential that the results from the ongoing OLE study and earlier studies may not be predictive of future results; the potential for the FDA’s earlier marketing approval of drugs other than FINTEPLA to cause the FDA to revoke Breakthrough Therapy designation; and other risks described in Zogenix's prior press releases as well as in public periodic filings with the Securities and 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.
Investors: Andrew McDonald
Founding Partner, LifeSci Advisors LLC
646-597-6987 | Andrew@lifesciadvisors.com
Media: Rachel Lipsitz
Public Relations, Syneos Health
858-449-9575 | email@example.com