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. 2021 Feb 24:21:76-82.
doi: 10.1016/j.omtm.2021.02.014. eCollection 2021 Jun 11.

Adeno-associated virus serotype 9 antibodies in patients screened for treatment with onasemnogene abeparvovec

John W Day  1 , Richard S Finkel  2   3 , Eugenio Mercuri  4 , Kathryn J Swoboda  5 , Melissa Menier  6 , Rudolf van Olden  6 , Sitra Tauscher-Wisniewski  6 , Jerry R Mendell  7   8
Affiliations

Adeno-associated virus serotype 9 antibodies in patients screened for treatment with onasemnogene abeparvovec

John W Day et al. Mol Ther Methods Clin Dev. .

Abstract

Spinal muscular atrophy is a progressive, recessively inherited monogenic neurologic disease, the genetic root cause of which is the 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.

Keywords: Adeno-associated virus serotype 9; antibody titers; clinical trials; enzyme-linked immunosorbent assay; gene replacement therapy; gene therapy; managed access programs; onasemnogene abeparvovec; spinal muscular atrophy; survival motor neuron.

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Conflict of interest statement

J.W.D. reports financial relationships with Novartis Gene Therapies, Inc., Affinia Therapeutics, Biogen, Cytokinetics, Ionis, Pfizer, Roche, and Sarepta, and royalties from Athena Diagnostics. R.S.F. has served as an advisor to Novartis Gene Therapies, Inc., Ionis, Biogen, and Roche, and received licensing fees from the Children’s Hospital of Philadelphia related to development of the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scale. E.M. has received personal compensation for clinical trial consulting and serving on scientific advisory boards from Novartis Gene Therapies, Inc. K.J.S. has received personal compensation from Novartis Gene Therapies, Inc., for serving as an advisory board member, and from Biogen for serving as a visiting professor; and has received research support from Novartis Gene Therapies, Inc., and Biogen-sponsored clinical trials. M.M. is an employee of Novartis Gene Therapies, Inc. R.v.O. and S.T.-W. are employees of Novartis Gene Therapies, Inc., and own Novartis stock or other equities. J.R.M. declares no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Testing frequency of patients with initially elevated anti-AAV9 antibody titers Patients who were initially excluded on the basis of elevated titers were retested for anti-AAV9 antibodies, when possible. Each line includes the total number of tests performed, and symbols mark the age at which a test was elevated (red X) or not elevated (green Ο). Patients were permitted to retest until they met the age limit set within the enrollment criteria. AAV9, adeno-associated virus serotype 9.
See this image and copyright information in PMC

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