2022 Volume 39 Issue 3 Pages 306-310
Recent progress in molecular biology has elucidated the pathogenesis of neurodegenerative diseases, including SBMA, and this progression has led new disease–modifying drug development being active. In Japan, Nusinersen for spinal muscular atrophy and Leuprorelin acetate for spinal and bulbar muscular atrophy were approved in August 2017, and now, it is expected that many new disease–modifying drugs for neurological diseases will be launched.
In neurodegenerative disease, we could hardly obtain sufficient information about the efficacy and safety of the drug before drug approval, so we should continuously collect clinical data after approval. We are now developing a real–world database to create new evoidence of leuprorelin acetate for SBMA. In this symposium, we will present two activities that are still in progress.
First, we are creating a new functional composite using real–world data to overcome the weakness of the existing outcome measurements. Based on the results of previous clinical studies on SBMA, we selected the following five quantitative measurements to be integrated into the functional composite : tongue pressure for bulbar function ; grip power for upper limb function ; timed walking test for lower limb function ; peak expiratory flow for truncal function ; and vital capacity for respiratory function. Using Z–score, we computed the following formula as SBMAFC ; SBMAFC = (Tongue Pressure (kPa) − 41.6)/7.84 + (Grip Power (kgw) − 45.0)/6.4 + (%PEF − 116.4)/22.4 + (Timed Walking speed (km/hr) − 7.7)/2.0 + (%FVC − 112.0)/11.8. In the comparison of SBMAFC with the existing rating scales, SBMAFRS and ALSFRS–R, the effect size of SBMAFC was the largest, suggesting that SBMAFC was the most sensitive to the disease progression. Second, we are analyzing the longitudinal data to estimate drug efficacy by comparing the data before and after drug administration. Further accumulation of longitudinal real–world data will enable the development of new real–world evidence for SBMA treatment.
The development of disease–modifying drug for neurodegenerative diseases will continue to be active. However, many barriers to success clinical trials, such as extremely small number of patients or slow progression, make it difficult to detect drug efficacy. So, often, we have insufficient evidence of efficacy or safety of the new drugs even after drug approval. Continuous clinical evaluations after approval are essential to establish a new drug profile.
