Adeno-Associated Virus Serotype 9 Antibodies in Patients Screened for Treatment with Onasemnogene Abeparvovec

Abstract Spinal muscular atrophy is a progressive, recessively inherited monogenic neurologic disease, the genetic root cause of which is absence of a functional survival motor neuron 1 gene. Onasemnogene abeparvovec (formerly AVXS-101) is an adeno-associated virus serotype 9 vector-based gene therapy that delivers a fully functional copy of the human survival motor neuron gene. We report anti–adeno-associated virus serotype 9 antibody titers for patients with spinal muscular atrophy when they were screened for eligibility in the onasemnogene abeparvovec clinical trials (intravenous and intrathecal administration) and Managed Access Programs (intravenous). Through December 31, 2019, 196 patients and 155 biologic mothers were screened for anti–adeno-associated virus serotype 9 binding antibodies with an enzyme-linked immunosorbent assay. Of these, 15 patients (7.7%) and 23 biologic mothers (14.8%) had titers >1:50 on their initial screening tests. Eleven patients (5.6%) had elevated titers on their final screening tests. The low percentage of patients with exclusionary antibody titers indicates that most infants with spinal muscular atrophy type 1 should be able to receive onasemnogene abeparvovec. Retesting may identify patients whose antibody titers later decrease to below the threshold for treatment, and retesting should be considered for patients with anti–adeno-associated virus serotype 9 antibody titers >1:50.