TY - JOUR T1 - Early experience with the FDA’s regulatory review of novel gene therapies JF - BMJ Evidence-Based Medicine JO - BMJ EBM DO - 10.1136/bmjebm-2021-111720 SP - bmjebm-2021-111720 AU - Jeremy Puthumana AU - Alexander C Egilman AU - Reshma Ramachandran AU - Nida Naushad AU - Nilay Shah AU - Joseph Ross Y1 - 2021/10/10 UR - http://ebm.bmj.com/content/early/2021/10/10/bmjebm-2021-111720.abstract N2 - Recent advances in gene therapies offer novel therapeutic options for many diseases that are otherwise resistant to pharmacologic treatment. Through gene therapy, scientists now have the opportunity to replace disease-causing genes with healthy copies, inactivate genes functioning improperly and introduce genes into the body to help fight disease.1 As of 31 December 2020, the US Food and Drug Administration (FDA) has approved five gene therapies, and more than 900 are in clinical development.2 Based on an assessment of the current pipeline, the FDA predicts it will approve 10–20 gene therapy products per year by 2025.3 In anticipation of many more approvals in the coming years, the FDA recently released final guidance documents on the clinical development and manufacturing of gene therapy products.2 To facilitate the development of these therapies, the 21st Century Cures Act introduced a new expedited development programme, the regenerative medicine advanced therapy (RMAT) designation. This programme grants all the benefits of the breakthrough therapy designation, including rolling review and intensive FDA guidance on efficient drug development, along with an expanded range of options to fulfil postapproval commitments.4 As of 31 December 2020, the FDA has granted RMAT designation to 58 products.5Although many laud these novel gene therapies as clinically transformative, there is growing concern about the high cost of these products, with list prices for one-time infusions ranging from $373 000 to as much as $2.1 million.6 In addition, gene therapies have been associated with serious safety risks including life-threatening immune responses and insertional mutagenesis-induced malignancies.7 As more gene therapies begin to enter the market, understanding the FDA’s past practices and standards in their review and approval of these products will help inform future regulatory decision-making, particularly upcoming approvals through the RMAT pathway, reimbursement decisions of payors, and the clinical … ER -