Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov;10(11):2155-2160.
doi: 10.1002/acn3.51889. Epub 2023 Sep 10.

Combination disease-modifying treatment in spinal muscular atrophy: A proposed classification

Crystal M Proud  1 , Eugenio Mercuri  2 , Richard S Finkel  3 , Janbernd Kirschner  4 , Darryl C De Vivo  5 , Francesco Muntoni  6   7 , Kayoko Saito  8 , Eduardo F Tizzano  9 , Isabelle Desguerre  10 , Susana Quijano-Roy  11 , Kamal Benguerba  12 , Dheeraj Raju  13 , Eric Faulkner  13   14   15 , Laurent Servais  16   17
Affiliations

Combination disease-modifying treatment in spinal muscular atrophy: A proposed classification

Crystal M Proud et al. Ann Clin Transl Neurol. 2023 Nov.

Abstract

We sought to devise a rational, systematic approach for defining/grouping survival motor neuron-targeted disease-modifying treatment (DMT) scenarios. The proposed classification is primarily based on a two-part differentiation: initial DMT, and persistence/discontinuation of subsequent DMT(s). Treatment categories were identified: monotherapy add-on, transient add-on, combination with onasemnogene abeparvovec, bridging to onasemnogene abeparvovec, and switching to onasemnogene abeparvovec. We validated this approach by applying the classification to the 443 patients currently in the RESTORE registry and explored the demographics of these different groups of patients. This work forms the basis to explore the safety and efficacy profile of the different combinations of DMT in SMA.

PubMed Disclaimer

Conflict of interest statement

CMP is a site principal investigator for Astellas, Biogen, Catabasis, CSL Behring, Novartis Gene Therapies, Inc., Pfizer, PTC, Sarepta, and Scholar Rock clinical trials, and has received honoraria for advisory board participation from Biogen, Novartis Gene Therapies, Inc., Novartis, Roche, and Sarepta; and speaker's fees from Biogen and Novartis Gene Therapies, Inc. EM has received personal compensation for clinical trial consulting, serving on scientific advisory boards, and research funding from Novartis Gene Therapies, Inc. RSF has received personal compensation for consulting and for advisory board participation from Novartis Gene Therapies, Inc., Biogen, Novartis, Roche, and Scholar Rock; editorial fees from Elsevier for co‐editing a neurology textbook; license fees from the Children's Hospital of Philadelphia; and research funding from Novartis Gene Therapies, Inc., Biogen, Roche/Genentech, and Scholar Rock. JK has received honoraria for clinical research and/or consultancy activities from Biogen, Novartis Gene Therapies, Inc., Pfizer, Roche, Sarepta and Scholar Rock. DCD has received personal compensation for consulting for advisory board participation from Novartis Gene Therapies, Inc., Biogen, Cytokinetics, Ionis Pharmaceuticals, Inc., Mallinckrodt, Metafora, PTC Therapeutics, Roche, Sanofi, Sarepta Therapeutics, and Ultragenyx, and the n‐lorem Foundation and SMA Foundation. He has no financial interests in these companies. He has received compensation as a consultant from Novartis Gene Therapies, Inc., Biogen, and Sarepta Therapeutics. He has received research grants from the Hope for Children Research Foundation, National Institutes of Health, SMA Foundation, Cure SMA, GliaPharm, Rocket Pharma, Glut1 Deficiency Foundation, and the US Department of Defense; he also has received clinical trial funding from Biogen, Mallinckrodt, PTC Therapeutics, Sarepta Therapeutics, Scholar Rock, and Ultragenyx; and serves as a member of the DSMB for Aspa Therapeutics. FM has received honoraria for scientific advisory board participation from Novartis Gene Therapies, Inc., Biogen, Novartis, Lilly, PTC, Roche, Dyne Therapeutics and Sarepta, and grants and personal fees from Novartis Gene Therapies, Inc., Biogen, and Roche. KS is a site principal investigator for Biogen, Novartis Gene Therapies, Inc., and Chugai/Roche clinical trials; has served on advisory boards for Novartis Gene Therapies, Inc./Novartis, Biogen, and Chugai/Roche; and has received speaker's fees from Biogen, Novartis, and Chugai/Roche. EFT has received personal compensation for consultancy from Novartis Gene Therapies, Inc., Biogen, Biologiz, Cytokinetics, Novartis, and Roche, and research funding from Biogen/Ionis and Roche. ID has received personal compensation for lectures and/or scientific board meetings from Novartis Gene Therapies, Inc., Biogen, BioMarin, PTC Therapeutics, and Sarepta. SQ‐R is a site principal investigator for clinical trials of Biogen and Novartis Gene Therapies, Inc.; has served as a consultant and has participated on advisory boards for Novartis Gene Therapies, Inc., Biogen, and Roche; and has received travel and speaker honoraria from Biogen, Novartis, and Roche. KB, DR, and EF are employees of Novartis Gene Therapies and own stock/other equities. LS has received personal compensation from Novartis Gene Therapies, Inc., Biogen, Inc., Biophytis, Cytokinetics, Dynacure, Roche, Santhera, and Sarepta Therapeutics, and research funding from Novartis Gene Therapies, Inc., Biogen, Dynacure, and Roche.

Figures

Figure 1
Figure 1
Proposed treatment terms and definitions and potential paths for patient identification and treatment. DMT, disease‐modifying treatment; N, nusinersen; OA, onasemnogene abeparvovec; R, risdiplam; SMA, spinal muscular atrophy. SMN, survival motor neuron. aNusinersen/risdiplam discontinued, or no doses of nusinersen/risdiplam received after onasemnogene abeparvovec infusion.
See this image and copyright information in PMC

References

    1. Finkel RS, Mercuri E, Meyer OH, et al. Diagnosis and management of spinal muscular atrophy: part 2: pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord. 2018;28(3):197‐207. - PubMed
    1. Mercuri E, Sumner CJ, Muntoni F, Darras BT, Finkel RS. Spinal muscular atrophy. Nat Rev Dis Primers. 2022;8(1):52. - PubMed
    1. Spinraza (nusinersen) [package insert]. Biogen, Inc.; 2020.
    1. Evrysdi (risdiplam) [package insert]. Genentech, Inc.; 2022.
    1. Zolgensma (onasemnogene abeparvovec‐xioi) [package insert]. Novartis Gene Therapies, Inc.; 2023.

Publication types