Aggregating genome sequencing and electronic health record data to accelerate rare disease drug development and market uptake

In the last 20 years, cost and turnaround time for whole genome sequencing (WGS) has decreased dramatically, while number of genetic diseases known molecular basis steadily increased, as investigational new drug applications gene-targeted therapeutics (GTT). GTTs have potential to transform outcomes in disorders by directly targeting causative defect. The United States Congress Food Drug Administration (FDA) implemented policies that are accelerating GTT development through Orphan Act recent guidelines GTTs, real-world evidence, surrogate endpoints. These stimulating hospitals partner with pharma aggregate WGS electronic health record (EHR) data. This is illustrated a Takeda-sponsored natural history study 175 boys Duchenne Becker Muscular Dystrophy utilising longitudinal EHR data from Rady Children’s Hospital. While predicted forced vital capacity (pFVC) values vary widely between patients, average pFVC pattern featured an initial 5-year improvement followed linear decrease. Multivariate modelling demonstrated increase was associated corticosteroid therapy, Hispanic had more rapid decline than non-Hispanic boys, exon-skipping oligonucleotide therapy did not change decline.