According to statements from the FDA, the Refusal to File (RTF) letter was issued because the NDA submitted by Zogenix on Feb. 5, 2019, lacked two important aspects:
- Some non-clinical studies were not included in the application, preventing the assessment of the chronic administration of fenfluramine hydrochloride (Fintepla’s active substance);
- One of the clinical datasets included in the application was incorrect, preventing the completion of the review process required for NDA filing.
The FDA has neither requested nor recommended the addition of new efficacy and safety data to complement the application.
Zogenix plans to seek guidance and work closely with the FDA to clarify the issues raised in the RTF letter, which will include the scheduling of a Type A meeting to discuss the situation and a new path forward.
“We remain highly confident in Fintepla’s clinical profile demonstrated in the Phase 3 program in Dravet syndrome and are committed to advancing the product candidate as a potential new treatment option for this and other rare and often catastrophic epileptic encephalopathies,” Stephen J. Farr, PhD, president and CEO of Zogenix, said in a press release.
“We are fully committed to working with the FDA as quickly as possible to address the open issues and clarify the path to successfully re-filing our application,” he said.
Fintepla is a low-dose oral solution of fenfluramine hydrochloride. Patients take it with other treatments to reduce the frequency of epileptic seizures. The therapy is being investigated in three Phase 3 clinical studies (ZX008-1501 NCT02682927, ZX008-1502 NCT02826863, and the open-label extension study NCT02823145).
Besides the NDA submission to the FDA, Zogenix also submitted a Marketing Authorization Application (MAA) for Fintepla for the same indication to the European Medicines Agency (EMA). The MAA has been accepted for review and the company expects to receive full approval by the beginning of 2020.
Meanwhile, Zogenix has entered into an exclusive distribution agreement with Nippon Shinyaku, a Japanese pharmaceutical company, to launch the distribution and commercialization of Fintepla in Japan. The company also plans to submit new drug applications to support the use of Fintepla for the treatment of people with Dravet syndrome and Lennox-Gastaut syndrome (LGS) in Japan.