In an article in The New England Journal of Medicine, Vinay Prasad and Martin Makary, two top US Food and Drug Administration officials, map out a new pathway for moving individualized genetic technologies into clinical practice. It is a tacit acknowledgment that the traditional scheme does not meet rare disease treatment needs in a timely way. The successful treatment of baby KJ, who was born with a rare genetic disorder, within a few months of diagnosis inspired this proposal.
Several features of baby KJ’s drug program will underlie the new pathway: identifying a specific molecular or cellular abnormality (in baby KJ’s case, a mutation in the carbamoyl phosphate synthetase 1 (CPS1) gene); targeting the biological alteration (a base editor corrected the mutation); knowing the natural history of the disease (progressive neurological damage following bouts of hyperammonemia); proving that the intended target is successfully edited; and evidence of clinical improvement. In baby KJ’s case, editing of the target was shown in mouse models, as it was considered too risky to biopsy his liver, and the child remains healthy seven months later.
