UCB, a global biopharmaceutical company, today announced that FINTEPLA®▼ (fenfluramine) oral solution has been approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for the treatment of seizures associated with Dravet syndrome as an add-on therapy to other anti-epileptic medicines for patients 2 years of age and older. (3) FINTEPLA® will be available at all Japanese hospitals and pharmacies.
Fenfluramine will be marketed by Nippon Shinyaku Co., Ltd. based on the exclusive sales agreement signed in 2019 between Zogenix Inc., (acquired by UCB in 2022) and Nippon Shinyaku Co., Ltd. UCB is now the Marketing Authorization holder.
“This approval in Japan delivers on our commitment towards expanding access to new treatment options to address unmet needs of those living with refractory epilepsy across the globe,” said Charl van Zyl, Executive Vice President, Neurology Solutions, UCB. “We would like to thank our Japanese patients and families for participating in the clinical trial and making this significant milestone happen so that more people with Dravet syndrome can help achieve their treatment goals.”
The MHLW approval was based a clinical trial program including data from a multi-national randomized, double-blind, placebo-controlled study of 143 children and young adults (2-18 years) with Dravet syndrome [that included trial participants from Japan], whose seizures were not adequately controlled with existing anti-epileptic medications. The study showed that when added to existing treatment regimens, those treated with 0.7 mg/kg day fenfluramine experienced a greater reduction (64.8%) in mean monthly convulsive seizures compared to placebo (P <.0001). The median age of patients in the study was 9 years (range, 2–18) and the average baseline convulsive seizure frequency across the study groups was approximately 63 seizures per month. Following a 6-week baseline observation period, patients were randomized to 1 of 3 treatment groups: 0.7 mg/kg per day (n = 49), 0.2 mg/kg per day (n = 46), or placebo (n = 48), in which fenfluramine or placebo was added to each patient’s current treatment regimen of anti-epileptic drugs. Patients were titrated to their target dose of fenfluramine over 2 weeks and then remained at that fixed dose for 12 weeks (26-mg maximum daily dose). (1)
The incidence of treatment-emergent adverse events was higher in the treatment groups as compared to the placebo group, with 91.7% (n=44) of patients in the 0.7 mg/kg/day group and 91.3% (n=42) of patients in the 0.2 mg/kg/day group experiencing at least one treatment-emergent adverse event compared to 83.3% (n=40) of patients in the placebo group. The incidence of serious adverse events was similar in all three groups with 6.3% (n=3) of patients in the 0.7 mg/kg/day group and 6.5% (n=3) of patients in the 0.2 mg/kg/day group experiencing at least one treatment-emergent serious adverse event compared to 4.2% (n=2) of patients in the placebo group, including one placebo patient who died due to SUDEP (sudden unexpected death in epilepsy). Prospective cardiac safety monitoring throughout the study showed that no study patients developed valvular heart disease or pulmonary arterial hypertension. (1)
As a condition of regulatory approval in Japan, UCB is required to undertake various post-marketing surveillance programs.
Approval supported by clinical trial data that showed when added to existing treatment regimens, fenfluramine significantly reduced monthly convulsive seizure frequency compared to placebo (1)
Approval highlights UCB's commitment to expanding global access to fenfluramine; an estimated 3,000 – 6,000 patients live with Dravet syndrome in Japan (2)
UCB Data on File. Sullivan, J. AES. 2020. Poster 853.
Yamada M, Suzuki K, Matsui D, Inoue Y, Ohtsuka Y. Long-term safety and effectiveness of stiripentol in patients with Dravet syndrome: Interim report of a post-marketing surveillance study in Japan. Epilepsy Res. 2021;170:106535.
Fintepla Japan PI. September 2022. フィンテプラ内用液2.2mg/mL (pmda.go.jp). Accessed September 2022