P.253 - Clinical orphan patient pool methodology estimates current patient pool in centronuclear myopathy

Abstract

Centronuclear myopathy (CNM) is a rare disease of inherited neuromuscular disorders, including X-linked CNM (XLCNM), autosomal dominant and recessive CNM, RYR1-related CNM. Review of the epidemiologic reports yielded limited incidence, prevalence and survival rate data. High variability between geographic regions and per disease etiology and severity resulted in limited insights in the current patient population. Currently, an incidence of 1 in 50000 births has been reported for severe, male XLCNM, and pediatric point prevalence of CNM has been estimated to be 1 in 100000, both known to underestimate the current pool. In support of clinical trial development, an integrated model linking the independent reports is required to obtain a better estimate of CNM patient numbers in function of age, etiology, and severity. To build the model, first an adapted CNM incidence estimate was calculated including moderate and mild XLCNM, female XLCNM patients and other etiologies (e.g. DNM2, BIN1, RYR1). Second, based on the analysis of the observed differences between the limited epidemiologic data, an estimate of current survival rates for each subpopulation was postulated. Next, the model integrates the specific relationships of reported incidence and prevalence data resulting in a patient flow based on the estimated survival for each subpopulation. The model was validated with reported subgroup prevalence and survival data. This methodology resulted in a model generating an estimate of the CNM pool per age, disease etiology and severity and per geography. The model estimates the incidence of the entire CNM population to be twofold the current reports on severe XLCNM alone and current patient numbers (2500 to 3000 in US and 1000 to 1500 in EU). In an orphan disease setting, this modelling methodology allows for a comprehensive assessment of the current CNM patient population, clinical trial development based on unmet need and fuels further epidemiologic discussion