Orphan Drugs and Their Impact on Pharmaceutical Development

High levels of productivity, with an increasing number of approvals for new molecular entities (NMEs) by the FDA during the past decade, have coincided with the emergence of innovative drugs for treatments of rare diseases that have utilized the FDA orphan drug program. Since 2000, NMEs with orphan designation encompass a significant portion of approved drugs and constitute about 80% of the approved drugs that have established novel human genome-encoded products in recent years. Biological approvals are also expanding, with 40% of the approved biological agents having orphan designation. This trend illustrates a pivot within the pharmaceutical industry: from research programs that focus on canonical blockbuster indications and targets, towards the establishment of new treatments for rare and difficult to treat diseases. Orphan drugs constitute more than 40% of all innovative pharmaceuticals that have expanded the human drug target landscape from 1983 to 2017. Our dataset encompasses 803 potentially new drug targets in clinical trials, of which 40% are under investigation as potential targets for treatment of rare diseases. Orphan drugs have reached as high as 55% of all FDA approved NMEs in 2014 and have maintained 43% to 44% of NMEs for 2015 to 2017. Biological approvals have come to comprise ∼20% of all newly approved NMEs, with 40% of biological NMEs having orphan designation. Cancer research is one of the primary drivers in pharmaceutical development, and 60% of the approved antineoplastic agents have orphan designations. Cancer development for orphan diseases is returning large sales, with four of the top five approved oncology products having not only orphan designation but also blockbuster status.