Little Impact on Children’s Height, Weight With Long-term Fintepla

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by Steve Bryson, PhD |

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Treatment for one year or longer with the antiseizure therapy Fintepla (fenfluramine) was shown to have a minimal impact on height and weight in children with Dravet syndrome, according to data from an open-label extension study.

Despite Fintepla’s active ingredient being fenfluramine — a medicine initially developed to suppress appetite — the data showed that children on long-term treatment had growth comparable to that of same-aged patients not on the therapy.

Moreover, the findings “suggest that most patients who initially lose appetite or weight eventually stabilize over time,” the researchers wrote.

However, the team suggested that body measurements should nonetheless be monitored during routine care for children on Fintepla treatment.

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The study, “Treatment with fenfluramine in patients with Dravet syndrome has no long-term effects on weight and growth,” was published in the journal Epilepsy & Behavior.

Fintepla is an approved add-on treatment for Dravet syndrome that has been shown to reduce the frequency of convulsive seizures in multiple clinical trials. Beyond seizures, Dravet patients experience developmental delays, cognitive impairment, short stature, and misaligned bones. Patients also may have hormonal problems that can lead to failure to thrive.

The active ingredient in Fintepla, fenfluramine, was initially developed as an appetite suppressant to control body weight in obesity. Consistently, Dravet patients enrolled in Fintepla clinical trials reported a reduced appetite.

Because of the therapy’s historical use to control weight, scientists at Zogenix, the company that developed Fintepla, and researchers at various hospitals in Europe and the U.S., wondered whether long-term Fintepla treatment impacted weight gain and growth in Dravet patients.

To find out, data were collected from eligible patients, ages 2 to 18, who completed clinical trials evaluating Fintepla and entered a three-year open-label extension (OLE) study (NCT02823145). All OLE participants started at a dose of 0.2 mg/kg/day and adjustments were made for efficacy from 0.2 to 0.7 mg/kg/day.

The most commonly prescribed antiseizure medications included Depacon (sodium valproate), Onfi (clobazam), Diacomit (stiripentol), Topamax (topiramate), Keppra (levetiracetam), and Klonopin (clonazepam).

At the time of this analysis, 279 participants had received Fintepla for at least one year and 128 for at least two years. The team extracted height and weight data at the beginning of the OLE (baseline) and after one year from 262 patients, and after two years from 110 patients.

Scientists then compared patients’ height and weight measurements to age-matched healthy individuals and Dravet patients not treated with Fintepla. The differences were reported as Z-scores, which reflected the deviation between the mean measurements from patients and healthy controls.

The analysis revealed the Z-score for height in Dravet patients before the OLE was -0.7, slightly below the mean height of healthy controls. After one year of Fintepla, the Z-score among patients was -0.8, and after two years, -0.7. For weight, the Z-scores also were similar after one year of Fintepla (-0.4 vs. -0.8) and two years (-0.5 vs. -1.0).

Thus, Fintepla treatment “resulted in minimal impact on height or weight over time in patients with available data,” the researchers wrote.

Height and weight Z-scores also were assessed at three Fintepla doses: 0.2 to less than 0.3 mg/kg/day, 0.3 to less than 0.5 mg/kg/day, and 0.5 to 0.7 mg/kg/day. No dose-dependent changes in height or weight from baseline were observed after one and two years.

Predicted height and weight percentiles over time were then calculated based on standardized growth charts of normal height and weight. Differences in Z-scores were minimal for Fintepla-treated individuals.

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Calculations predicted that patients treated with Fintepla for one year or more had an estimated change in Z-score per year of -0.056 for height and -0.166 for weight. For participants with three height and weight measurements (at baseline, one and two years), Z-score per year was estimated to change -0.025 for height and -0.188 for weight.

Predicted height and weight for a child started on Fintepla at age 8, following 0.5-, one-, and two years of treatment, were compared with published data in Dravet patients whose therapy did not include Fintepla.

Changes in Z-scores for height and weight in children after one and two years of Fintepla were similar to predictions of those without the therapy, “suggesting that [Fintepla] treatment did not further impair growth and development in these children” with Dravet syndrome, the researchers added.

During the OLE, standard clinical practices helped manage decreased appetite and weight loss in these patients. Interventions included increasing calorie-dense foods and caloric consumption, eliminating low-fat foods, and additional nutritional supplements.

Temporary gastric tubing with medication adjustments was considered with persistent weight loss. In addition, the therapeutic levels of antiseizure medicines were monitored and adjusted to balance seizure control with weight and growth.

“Our data demonstrate that long-term treatment with [Fintepla] in patients with [Dravet syndrome] resulted in minimal impact on weight and growth over that expected in a population of patients with [Dravet syndrome],” the authors concluded. “Anthropomorphic parameters [body measurements] should be monitored, and appropriate interventions taken, during routine clinical care of these patients.”