With this decision, Zogenix will be able to market Fintepla in all European Union (EU) member states, plus the United Kingdom, Iceland, Norway, and Liechtenstein. The first EU launch is planned for Germany in early 2021.
The U.S. Food and Drug Administration (FDA) approved Fintepla for the same indication in June.
“With the EC approval in place, we can now begin making FINTEPLA more widely available for the treatment of Dravet syndrome patients in Europe who seek new safe and effective treatment options,” Stephen Farr, PhD, president and CEO of Zogenix, said in a press release.
Fintepla is an oral, low-dose solution of fenfluramine hydrochloride — an amphetamine derivative that has appetite-suppressant properties — and works by blocking the re-uptake of serotonin, an important neurotransmitter (or chemical messenger) that supports communication between nerve cells.
Recent research also suggests that Fintepla may act on sigma receptors, a type of cell membrane receptor commonly found in nerve cells.
Fintepla’s approval was based on positive safety and efficacy results from two randomized Phase 3 trials — ZX008-1501 (NCT02682927) and ZX008-1502 (NCT02826863) — as well as interim findings from an open-label extension study (NCT02823145) in 330 Dravet patients. The ZX008-1502 study is still recruiting eligible patients at clinical sites across Japan; information is available here.
The Phase 3 trials enrolled children ages 2 to 18, and compared two dosages of Fintepla — 0.7 mg/kg/day, and 0.2 mg/kg/day — with a placebo. Treatment occurred over 14 weeks, including an initial two-week titration period to reach the assigned dosage.
The trials’ primary goal was to assess Fintepla’s effectiveness at high dose in lowering the frequency of participants’ convulsive seizures compared with placebo patients. Secondary outcomes included the change in seizure frequency among those on the lower dose, as well as overall changes in seizure severity, and the safety and tolerability of Fintepla.
Results showed that, when given at its higher dose, Fintepla significantly reduced the frequency of convulsive seizures in children and young adults whose seizures were not adequately controlled by existing medications, including Diacomit (stiripentol).
These reductions occurred within three to four weeks of treatment, and remained stable over the 14- to 15-week treatment periods.
Moreover, results from the open-label extension study show that Fintepla provided a sustained and meaningful reduction in convulsive seizure frequency among young children with Dravet syndrome, with similar efficacy to that seen in older patient groups.
“Experience from clinical studies has shown that FINTEPLA offers an impressive reduction in seizures, plus an improvement in quality of life. In conjunction with the ongoing data being collected on the safety profile of the therapy, FINTEPLA represents an effective new treatment option,” said Tilman Polster, MD, PhD, a pediatric epilepsy specialist at the Mara Hospital of the Bethel Epilepsy Centre in Bielefeld, Germany, and primary investigator for these Dravet trials in that country.
“Current treatments for Dravet syndrome are unsatisfactory, resulting in the disease affecting motor and mental development,” Polster added.
The most frequent side effects noted in the trials consisted of loss of appetite, diarrhea, fever, fatigue, upper respiratory tract infection, lethargy, drowsiness, and bronchitis.
Because Fintepla’s active ingredient, fenfluramine, was removed from the market in 1997 after some patients experienced cardiac valvulopathy (disease of the heart’s valves) and pulmonary arterial hypertension, its labeling includes a warning about these possible side effects.
No cardiovascular complications were reported during the trials, but these potential complications require patients to undergo cardiac monitoring by echocardiogram before treatment, every six months during treatment, and three to six months after treatment for the possibility of cardiac abnormalities.
Fintepla will be available under a controlled access program requested by the European Medicines Agency to prevent off-label use for weight management, and to confirm that physicians have been informed of the need for a patient’s periodic cardiac monitoring.
Zogenix will also conduct the Fintepla Registry, an observational registry to provide data on Fintepla’s long-term safety and the frequency of echocardiographic patient monitoring.
In addition to Dravet, Fintepla is being evaluated for the treatment of seizures associated with other rare epilepsies, such as Lennox-Gastaut syndrome.
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