Abstract Details

Title Long-Term Cardiovascular Safety of Fenfluramine for Lennox-Gastaut Syndrome: Interim Analysis of Open-Label Safety Study

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S24 - Epilepsy/Clinical Neurophysiology (EEG): Clinical Epilepsy (4:18 PM-4:30 PM)

Poster/Presentation
Number 005

Background Over a treatment duration of 3-12 months, FFA has demonstrated sustained reduction (39.4%-51.8%) in frequency of seizures associated with a fall in LGS patients. FFA was recently approved for treatment of Dravet syndrome (DS). No valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) was observed in DS patients with FFA treatment up to 3 years.

Objective To report the first long-term cardiovascular safety findings from an interim analysis of an open-label safety extension (OLE) study of fenfluramine (FFA) for treatment of Lennox-Gastaut syndrome (LGS).

Design/Methods Eligible patients with LGS who completed a 14-week randomized controlled trial (RCT) enrolled in the OLE (NCT03355209). Patients with current cardiac VHD, PAH, or any degree of aortic (AV) or mitral valve (MV) regurgitation were excluded from entering the RCT. All patients in the OLE were started on 0.2mg/kg/day FFA, titrated for effectiveness and tolerability after 1 month (max 0.7mg/kg/day; 26mg/day). Cardiac valve function and pulmonary artery systolic pressure were assessed by standardized transthoracic Doppler echocardiography at OLE baseline; at Months 1, 3, 6, and 9; at end of study; and 3-6 months after study exit. Safety was assessed, including presence of VHD or PAH.

Results 247 patients enrolled by 19-Oct-2020 and received ≥1 dose of FFA; median duration of exposure was 364 days (range, 19-542 days). Mean age was 14.3±7.6 years (79 [32%] adults, 18-36 years). 82 (33.2%) discontinued, mostly for lack of efficacy (55). No clinically significant changes in mitral or aortic valve MV/AV function indicative of VHD or findings indicative of PAH were observed.

Conclusions OLE results demonstrate no VHD or PAH after daily treatment with FFA for median exposure of 364 days in children and adult patients with LGS, thereby supporting the safety of FFA as a treatment option for LGS patients.

Authors/Disclosures
Pierre Wong, MD (Children's Hospital Los Angeles) PRESENTER	Dr. Wong has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zogenix. Dr. Wong has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for NorCal/Kaiser. Dr. Wong has received publishing royalties from a publication relating to health care.
Anupam Agarwal, MD (Zogenix)	Dr. Agarwal has received personal compensation for serving as an employee of ZOGENIX.
Gail M. Farfel, PhD	Dr. Farfel has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Durect Corp. Dr. Farfel has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Zogenix. Dr. Farfel has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for AvroBio. Dr. Farfel has received intellectual property interests from a discovery or technology relating to health care.
Arnold Gammaitoni, PharmD (Zogenix)	Dr. Gammaitoni has received personal compensation for serving as an employee of Zogenix Inc.. Dr. Gammaitoni has received stock or an ownership interest from Zogenix Inc..
	No disclosure on file
	No disclosure on file