Figure 1: Ideal AAV gene therapy development timeline

Adenoassociated virus (AAV) vectors have emerged as the prominent delivery mechanisms of corrective gene therapies. Three such products — Glybera (alipogene tiparvovec, uniQure), Luxturna (voretigene neparvovec-rzyl, Spark Therapeutics), and Zolgensma (onasemnogene abeparvovec-xioi, AveXis) — have been licensed, and a growing number of candidates are entering late-stage development. In mapping out an AAV gene therapy product development strategy, biomanufacturers should address fundamental considerations for their manufacturing strategies for both phase 1–2 clinical evaluation and translation for commercial market supply. A manufacturing strategy encompasses a supply chain of critical raw materials, a cell-substrate manufacturing platform, and a decision either to outsource manufacturing to contract development and manufacturing organizations (CDMOs) or to establish internal manufacturing capabilities. Herein we provide a snapshot of some key options and variables and their potential impacts on AAV vector manufacturing.

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Corresponding author Joseph Rininger (jarininger@lathambiopharm.com) is director of cell and gene therapy, Ashley Fennell is associate consultant, Lauren Schoukroun-Barnes is senior associate consultant, and Joshua Speidel is managing director, all at Latham Biopharm Group, 101 Main Street, Suite 1400, Cambridge, MA 02142.