The U.S. Food and Drug Administration has issued the draft guidance “Nonclinical Testing of Individualized Antisense Oligonucleotide (ASO) Drug Products for Severely Debilitating or Life-Threatening Diseases - Guidance for Sponsor-Investigators.” Due to advances in genetic testing and molecular diagnosis, in some circumstances, it is possible to identify the precise genetic cause of a specific patient’s disease and develop an ASO drug product that is tailored to the patient’s specific genetic variant. These advances provide an opportunity for new approaches to drug development.

This draft guidance defines the nonclinical information required to support an investigational new drug (IND) application for antisense oligonucleotides being developed to treat a severely debilitating or life-threatening disease caused by a unique genetic variant that affects only a small number of patients identified for treatment. However, this draft guidance will not address nonclinical testing for commercial development of oligonucleotides.

This guidance is the second in a series of FDA guidances intended to represent the initial steps FDA is taking to clarify the pathway for the development of individualized drug products. The first of these such guidances, IND Submissions for Individualized Antisense Oligonucleotide Drug Products: Administrative and Procedural Recommendations - Guidance for Sponsor-Investigators, published in January 2021.

FDA is accepting comments and suggestions on this draft guidance.