Clinical trial data back benefits of LGS seizure med, analysis finds
Fintepla rapidly cuts seizure frequency, with greatest benefits a few months out
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Data analysis from a clinical trial showed the benefits of Fintepla.
Fintepla (fenfluramine) can rapidly reduce seizure frequency in people with Lennox–Gastaut syndrome (LGS), with the greatest benefits typically appearing after a few months of treatment and common side effects often becoming less noticeable over time, according to a post hoc analysis of Phase 3 clinical data.
“Patients, parents, and doctors should be aware of this time course to allow [Fintepla] enough time to work,” researchers said. The study, “Changes in effectiveness and safety in patients with Lennox–Gastaut syndrome transitioning from the fenfluramine randomized controlled trial to open-label extension study,” was published in Epilepsia Open.
Symptoms of LGS include frequent seizures that are often difficult to control with standard anti-seizure medications. Fintepla, a treatment from UCB approved to reduce seizures in patients ages 2 and older, works by increasing the release of serotonin, a chemical that helps nerve cells communicate, and by calming the overactive signals that cause seizures.
“LGS remains one of the most challenging rare epilepsies to manage, and families and clinicians often have limited visibility into what response may look like in the first months of treatment,” Hugo Xi, MD, head of medical affairs for epilepsy and rare syndromes at UCB, said in a company press release. “These findings provide important insight into the treatment trajectory of Fintepla, helping inform conversations around early response, dose titration, and the potential value of continued treatment over time.”
14-week trial, extension study
The researchers analyzed data from a Phase 3 clinical trial (NCT03355209) in which patients were randomly assigned to receive either Fintepla or a placebo for 14 weeks. Almost all patients (93.9%) then entered an open-label extension in which they received Fintepla. The post hoc analysis covered 151 patients who completed at least one year of open-label treatment.
Of the 151 patients, 59 had received a placebo before switching to Fintepla, while 92 received Fintepla throughout both the randomized and open-label parts. Patients continued taking a median of three other anti-seizure medications. The average daily dose of Fintepla gradually increased from 0.2 mg/kg to 0.5 mg/kg over four months, then remained about the same for the rest of the 12 months. The greatest benefits occurred after patients reached these higher, maintenance doses.
The researchers mainly measured seizures associated with falls, sometimes called drop seizures, which are especially dangerous because they can cause serious injuries. They also counted seizure-free days and assessed overall daily functioning using the Clinical Global Impression–Improvement (CGI-I) scale, which rates the extent to which a patient’s health has improved since treatment began.
Patients who switched from the placebo to Fintepla showed a rapid reduction in seizures. After one month of treatment, the median number of seizures associated with a fall had decreased by 32.1% compared with before treatment. As the dose gradually increased, the median number of seizures associated with a fall decreased by 48.2%.
Patients who had been taking Fintepla before entering the open-label extension maintained the treatment’s benefits. Seizures became 48.5% less frequent after the first month and remained 44.2% to 46% less frequent over the following months. By the fourth to sixth month, patients who switched from the placebo to Fintepla gained an average of 6.2 seizure-free days per month. Those who took Fintepla alone gained 5.1 seizure-free days per month.
Daily functioning also improved. After 12 months, about half of the patients in both groups were rated by parents, caregivers, and doctors as “much improved” or “very much improved” on the CGI-I scale. “These results emphasize advantages of sustained use, adequate dose titration, and underscore benefits that extend beyond seizure reduction,” the researchers wrote.
Among patients who switched from a placebo to Fintepla, common side effects became more frequent after treatment began. These included decreased appetite, sleepiness, tiredness, diarrhea, fever, and nasopharyngitis, an infection affecting the nose and throat.
For patients who had been taking Fintepla, common side effects became less frequent over time, and included decreased appetite, sleepiness, tiredness, and diarrhea. This suggests that many side effects may lessen as treatment continues, supporting the medication’s long-term tolerability, the researchers said.
“In clinical practice, assessment of [Fintepla] effectiveness should extend to [four or more] months of treatment if possible,” they wrote.
