Authors :
Carla Schad, MD – UCB; Shikha Polega, PharmD – Zogenix, Inc. (now a part of UCB); Kevin Rohrbach, MD – Zogenix, Inc. (now a part of UCB); Sarah Maxey, MA – Zogenix, Inc. (now a part of UCB); Hunter Liggett, BS – Zogenix, Inc. (now a part of UCB); Amélie Lothe, PhD – Zogenix International (now a part of UCB)
This is a Late Breaking abstractRationale: While randomized controlled trials are the gold standard for evidence-based medicine, study protocols are rigorous, and results may not be generalizable to the clinical practice setting. Real-world evidence (RWE) studies are conducted to complement clinical trial data and describe the use of medication(s) in routine clinical practice. Fenfluramine (FINTEPLA
®, FFA) was FDA-approved for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients ≥ 2 years old in 2020 and 2022, respectively, and has a dual-action mechanism of serotonergic activity and sigma-1 receptor positive modulation. This RWE study compares FFA discontinuation rates between U.S. specialty pharmacy records to the combined results from the open-label extension (OLE) studies in patients with DS and LGS.
Methods: The FINTEPLA Risk Evaluation and Mitigation Strategies (REMS) program is a restricted distribution model in the US that certified one outpatient specialty pharmacy. Pharmacy records of patients prescribed FFA for DS or LGS that was discontinued at any time from July 1, 2020, through June 30, 2022, were obtained. The number of patients who were actively being shipped FFA, number of patients who discontinued therapy, reasons for discontinuation (DC), patient demographics, mean FFA dose at time of DC and median duration of treatment (exposure) were reported. Descriptive statistics were used to analyze the data.
Results: During the period evaluated, a total of 1206 patients with an indication for DS or LGS obtained FFA from the specialty pharmacy and 226 (18.7%) later discontinued treatment (184 DS, 42 LGS). This compared to a 32.1% DC rate in the combined OLE studies (Table). In this analysis, most discontinued patients (91.6%) were treatment naïve. Mean approximate age ± SD was 13.7 ± 7.2 years and 57.1% were male; mean total daily dose ± SD during treatment was 0.44 mg/kg/day ± 0.18 (range, 0.09-1.01). In the cohort where FFA was discontinued, 61 patients were prescribed daily regimens > 24.5 mg, approaching the FDA recommended capped dose of 26 mg. Median treatment duration in the patients who discontinued FFA was 142.5 days (range, 13-631). Out of all patients (N=1206), the most common primary reasons for DC included lack of efficacy and side effects, which occurred in 108 (9.0%) and 71 (5.9%) patients, respectively. These were also the most common reasons for DC in the combined OLE studies of DS and LGS (17.9% and 4.2%; Figure). Discontinuation due to patient or caregiver request occurred in 4.9% of OLE patients, compared to 1.1% of real-world patients.
Conclusions: This RWE study complements results from the OLE studies of DS and LGS. This analysis demonstrated that overall discontinuation rates among real-world patients prescribed FFA for DS or LGS occurred less than what was reported in the OLE studies. Rates of DC secondary to side effects were low and comparable. Although lack of efficacy continues to be the most common reason for stopping FFA, this was reported less frequently in routine clinical practice.
Funding: Funded by Zogenix, Inc. (now a part of UCB)