New Financial and Research Models for Pediatric Orphan Drug Development: Focus on the NCATS TRND Program

While there are approximately 7,000 identified human diseases considered as ‘rare’ based on population prevalence or incidence, the cumulative impact runs into the millions of patients globally. Although the genetic underpinnings of more than 2,000 rare diseases have been elucidated, there remains a paucity of therapeutic options, frequently due to lack of commercial interest. Development programs suffer high attrition within the so-called ‘Valley of Death,’ in which the risks of scientific failure are still too high to justify the increasing development costs. This problem is common to any drug development campaign, but particularly exacerbated in the rare diseases, many of which arise in childhood. To stimulate development of therapeutics for these otherwise under-served patient populations, a number of regulatory incentives and research initiatives have been established. Extended patent protections, expedited regulatory reviews for qualified drug sponsors, and clinical trial grant support aim to foster interest in completing development programs. To stimulate researchers to embark on rare disease drug development campaigns, earlier-stage preclinical research resources have also been created, such as the Therapeutics for Rare and Neglected Diseases (TRND) program at the US National Institutes of Health (NIH). TRND is a unique NIH program created to support drug development through formation of public–private partnerships. These partnerships leverage the robust biopharmaceutical industry experience of the TRND staff scientists and the deep disease area expertise of the collaborating partners. Each project adopted into the TRND portfolio aims to satisfy two broad goals: developing a novel therapy for a rare or otherwise neglected disease, and exploring ways to accelerate the drug development process overall so that lessons learned can be disseminated to the wider community undertaking translational research. This article discusses common obstacles and opportunities for therapeutic development, and provides examples of the types of projects TRND has undertaken across a broad range of pediatric rare disorders.