Moving away from one disease at a time: Screening, trial design, and regulatory implications of novel platform technologies

Abstract

Most rare diseases are caused by single‐gene mutations, and as such, lend themselves to a host of new gene‐targeted therapies and technologies including antisense oligonucleotides, phosphomorpholinos, small interfering RNAs, and a variety of gene delivery and gene editing systems. Early successes are encouraging, however, given the substantial number of distinct rare diseases, the ability to scale these successes will be unsustainable without new development efficiencies. Herein, we discuss the need for genomic newborn screening to match pace with the growing development of targeted therapeutics and ability to rapidly develop individualized therapies for rare variants. We offer approaches to move beyond conventional “one disease at a time” preclinical and clinical drug development and discuss planned regulatory innovations that are necessary to speed therapy delivery to individuals in need. These proposals leverage the shared properties of platform classes of therapeutics and innovative trial designs including master and platform protocols to better serve patients and accelerate drug development. Ultimately, there are risks to these novel approaches; however, we believe that close partnership and transparency between health authorities, patients, researchers, and drug developers present the path forward to overcome these challenges and deliver on the promise of gene‐targeted therapies for rare diseases.

The Rare Diseases Clinical Research Network: a model for clinical trial readiness

“…Finally, the value of considering groups of conditions together, despite regulatory challenges, rather than the current system of focusing on one rare disease at a time. 55 progress and future directions.…”

The future of commercial genetic testing

“…Although many issues around population genomic screening have been discussed, the relatively high price of sequencing has largely restricted these activities to a research-only or theoretical space. As the cost of sequencing drops, the number of sequencing-based screening programmes is likely to increase, and their scope (the amount of conditions they involve and the number of individuals screened) will expand [23,24 ▪▪ ].…”

The continuing challenges facing gene‐targeted therapies

“…Only through innovative, collaborative efforts will we achieve this goal for children and families with neurogenetic disorders. 5…”

“…Because each answer begets another question and because a fuller understanding reveals the unimaginable complexity of biological systems, there is much work yet to be done to safely effect cures. Only through innovative, collaborative efforts will we achieve this goal for children and families with neurogenetic disorders 5 …”