Dr Bradley GalerBradley Galer, MD
Recently, Zogenix completed its submission of a New Drug Application (NDA) for ZX008, its low-dose fenfluramine agent, for the treatment of seizures associated with Dravet syndrome.

The therapy, which is also being studied for Lennox-Gastaut syndrome, is being marketed as Fintepla. It is a serotonergic agent, which makes it the only antiepileptic agent of its kind currently being developed. Thus far, a pair of phase 3 trials in Dravet syndrome, as well as an interim analysis from the company’s ongoing open-label extension study, have been conducted to support the NDA. The open-label extension includes 232 patients being treated for up to 21 months with ZX008.

At the American Epilepsy Society’s 2018 annual meeting in New Orleans, Louisiana, NeurologyLive spoke with Joseph Sullivan, MD, the director of the Pediatric Epilepsy Center at UCSF’s Benioff Children’s Hospital and an investigator in ZX008’s clinical development program, about the treatment’s potential. He pointed out the positive signs regarding executive function improvements for the children treated with ZX008 as an additional piece of the therapy’s promise.

To find out more about the therapy and what the clinical community should know following this NDA submission, NeurologyLive spoke with Bradley Galer, MD, the executive vice president and chief medical officer of Zogenix.

NeurologyLive: What sets Fintepla apart from other medicines for Dravet? 

Bradley Galer, MD: Our phase 3 data demonstrate robust, clinically meaningful, and durable convulsive seizure reduction rates in Dravet syndrome. We believe that FINTEPLA’S improvements seen in our studies represent a significant potential advancement for patients with Dravet syndrome who urgently need effective treatments. 

What’s the most encouraging piece of data that’s been demonstrated in its clinical development?

The consistency and durability of significant seizure reduction as seen in all phase 3 studies.
 
For instance, the interim analysis of data from our ongoing open-label extension study, which included 232 patients treated for a median 256 days, demonstrated 64.4% of patients experienced a greater than 50% reduction in convulsive seizure frequency, and 41.2% of patients experienced a greater than 75% reduction in convulsive seizure frequency.
 
Moreover, in Study 1 a total of 10 patients (25%) in the 0.8 mg/kg group and five patients (13%) in the 0.2 mg/kg group experienced either zero seizures or only one single seizure during the entire treatment period, as compared to zero patients in the placebo group. The average number of convulsive seizures before treatment was approximately 40 per month.

What do clinicians need to know about the agent ahead of its potential approval?

We are extremely pleased with the efficacy and safety profile demonstrated across both Phase 3 trials and our ongoing open-label extension (OLE) study of FINTEPLA. Our interim analysis of the OLE study of FINTEPLA confirms these results are sustained over time, with some patients being treated for up to two years. The occurrence of adverse events was consistent across both Phase 3 placebo-controlled studies and the open-label extension study with no patient developing cardiac valvulopathy or pulmonary hypertension at any time.

Physicians and parents continue to be pleased with the efficacy and safety profile of FINTEPLA, demonstrated by the fact that approximately 90% of patients in our interim analysis remained in the OLE study.

Transcript edited for clarity.
REFERENCES
Zogenix Submits New Drug Application to U.S. Food & Drug Administration and Marketing Authorization Application to European Medicines Agency for FINTEPLA® for the Treatment of Dravet Syndrome [press release]. Emeryville, CA: Zogenic, Inc; Published February 6, 2019. globenewswire.com/news-release/2019/02/06/1711347/0/en/Zogenix-Submits-New-Drug-Application-to-U-S-Food-Drug-Administration-and-Marketing-Authorization-Application-to-European-Medicines-Agency-for-FINTEPLA-for-the-Treatment-of-Dravet-S.html. Accessed February 6, 2019.