With eye on winning over FDA in the wake of RTF, Zogenix publishes new Fintepla data
Battered by a refuse-to-file letter from the FDA in April, Zogenix has made strides to convince the FDA that its Dravet syndrome drug is worth approval. Last month, the regulator accepted its resubmitted application to market Fintepla, one half of the notorious axed prescription weight-loss cocktail fen–phen, for patients with the rare, severe form of childhood epilepsy.
Earlier this week, data from a Zogenix-funded 119-patient study led by researchers from UCSF, University of Leuven and other treatment centers showed that Fintepla, known chemically as fenfluramine, helped cut convulsive seizures by 62% versus placebo in patients with Dravet syndrome.
In the trial, two doses of Fintepla were tested. The higher dose induced the 62% reduction, while the smaller dose induced a 32% cut in seizures versus placebo. The longest seizure-free interval, on average, was 25 days for the higher-dose group, 15 for the lower-dose group, and 9 days for placebo.
Patients enrolled in the trial had an average of 40 convulsive seizures in the month before the trial, despite their existing treatment regimen. Roughly 10% to 15% of Dravet syndrome patients die by the age of 25 due to seizure-triggered irregular heart rhythm or suffocation.
On the safety side, most side-effects were mild-to-moderate and occurred across the three arms of the trial and no cases of pulmonary arterial hypertension or “clinically significant” signs or symptoms of cardiovascular disease were observed in the 14-week trial, nor in the ongoing open-label extension trial, in which some patients have been taking the drug for more than one year.
However, weight-loss was a side effect of note in both the Fintepla arms. In the higher dose group, 8/40 patients lost 7.2% to 11.4% of their body weight, while in the smaller dose group, 5/39 patients experienced weight loss that ranged from 8.4% to 21.9% of their body weight. Other adverse events associated with the drug were decreased appetite, diarrhea, lethargy, and somnolence.
“Our conclusions about the cardiovascular safety of fenfluramine are limited by the short treatment and observation period of 14 weeks in this trial,” the authors wrote in the journal Lancet. “These findings are consistent with those reported with long-term use of fenfluramine at doses between 0·13–0·69 mg/kg per day in Dravet syndrome in Belgium, where no cases of valve dysfunction or pulmonary hypertension have been reported with up to 30 years of fenfluramine treatment with ongoing echocardiographic examinations.”
The diet drug fen-phen — a formulation of an appetite depressant and a type of amphetamine — was once deemed a silver bullet for the burgeoning obesity crisis. But it was taken off US shelves in 1997 after fresh data showed it could cause heart valve defects in as many as a third of patients. In Belgium, fenfluramine has been approved for compassionate use since 2002.
In April, Zogenix said the FDA had rebuffed reviewing Fintepla’s marketing application, citing the lack of certain non-clinical studies key for the assessment of chronic administration of the drug as well as an incorrect version of a clinical dataset. Last month, the FDA accepted Zogenix’s revamped application. The agency is expected to make its final decision by March 25.
If approved, Fintepla will compete with GW Pharmaceuticals’ pioneering cannabis-derived Epidiolex, which is pitted as a blockbuster, as well as Biocodex’s Diacomit.
Meanwhile, Fintepla is also under investigation for use in Lennox-Gastaut syndrome. Late-stage data from a Phase III study is expected in early 2020.