NUMBER NEEDED TO TREAT (NNT) WITH FENFLURAMINE TO ACHIEVE A CLINICALLY MEANINGFUL REDUCTION IN CONVULSIVE SEIZURE FREQUENCY IN PATIENTS WITH DRAVET SYNDROME: HEALTH ECONOMIC IMPLICATIONS
Author(s)
Sullivan J1, Dlugos D2, Nabbout R3, Haney D4, Morrison G5, Farfel GM5, Galer BS5, Gammaitoni A5
1University of California San Francisco, San Francisco, CA, USA, 2Children’s Hospital of Philadelphia, Philadelphia, CA, USA, 3Centre de Référence Epilepsies Rares (CReER), Hôpital Universitaire Necker - Enfants Malades, Paris, France, 4Zogenix Consultant, Burlingame, CA, USA, 5Zogenix, Inc., Emeryville, CA, USA
Presentation Documents
OBJECTIVES: Families of patients with Dravet syndrome (DS) experience substantial financial and humanistic burdens, driven by seizures and poor neurodevelopmental outcomes. We determined the number needed to treat (NNT) with fenfluramine to achieve “clinically meaningful” reductions in monthly convulsive seizure frequency (MCSF), as determined by Clinical Global Impression of Improvement (CGI-I) ratings and improvement on Behavior Rating Inventory for Executive Function (BRIEF®2) Index Scores. METHODS: Using data from a Phase 3 and long-term extension study for adjunctive fenfluramine (NCT02682927/NCT02826863/NCT02823145), we assessed: (1) the degree of seizure frequency reduction associated with “Very much improved” caregiver CGI-I ratings via receiver operating characteristic (ROC) analysis and (2) the proportion of patients with clinically meaningful, ≥10-point improvement on BRIEF®2 index scores (Behavior, Emotion, Cognition, Global), comparing patients with <25% (negligible) vs ≥75% (profound) MCSF reduction via 2-sided Mann-Whitney-U test. NNT was calculated: 1/((Experimental-Responder Rate)-(Control-Responder Rate)). RESULTS: ROC analysis of CGI-I ratings identified a clinically meaningful threshold of ≥60% MCSF reduction. There was ≥60% MCSF reduction in 60%, 28% and 5% of patients in fenfluramine 0.7 mg/kg/day (NNT=2), fenfluramine 0.2 mg/kg/day (NNT=4), and placebo groups. Patients with ≥75% MCSF reduction were significantly more likely to achieve ≥10-point improvements in Emotion Regulation and Global BRIEF®2 Index Scores at Year 1; 45%, 20%, and 2% of patients in fenfluramine 0.7 mg/kg/day (NNT=2), fenfluramine 0.2 mg/kg/d (NNT=6), and placebo groups achieved ≥75% MCSF reduction. CONCLUSIONS: Fenfluramine treatment resulted in NNT=2 to achieve either clinically meaningful (≥60%) or profound (≥75%) MSCF reductions; profound reductions were associated with executive-function improvements. Prior DS antiepileptic-drug studies report NNT=5-6 for only ≥50% MCSF reduction. Published average annual healthcare utilization costs for DS are ~$27,276, plus ≥$80,000 (indirect). An NNT=2 to achieve clinically meaningful outcomes may have important positive health economic implications for both payers and patients/caregivers vs currently available treatment options.
Conference/Value in Health Info
2020-05, ISPOR 2020, Orlando, FL, USA
Value in Health, Volume 23, Issue 5, S1 (May 2020)
Code
PIH4
Topic
Clinical Outcomes, Economic Evaluation
Topic Subcategory
Comparative Effectiveness or Efficacy, Trial-Based Economic Evaluation
Disease
Neurological Disorders, Pediatrics