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Splicing Modifiers and Gene Therapy for SMA
Panelists discuss how splice modifiers work by enhancing protein production from the SMN2 gene, with risdiplam (Evrysdi) being an oral daily medication and nusinersen (Spinraza) being administered intrathecally quarterly, both showing similar safety and efficacy profiles.
EP: 1.Describing SMA Progression Over Time
EP: 2.Unmet Needs of Older Patients Living With SMA
EP: 3.Examining the Importance of Early Treatment for SMA
EP: 4.Key Functional Milestones Affected by Disease Progression
EP: 5.The Importance of Supportive Care for Patients Living With SMA
EP: 6.Introduction to Therapies Used to Treat SMA
EP: 7.Splicing Modifiers and Gene Therapy for SMA
EP: 8.Key Clinical Considerations for the Management of SMA
EP: 9.Assessing Different Factors When Selecting a Treatment
EP: 10.Evaluating the Potential of Intrathecal Gene Therapy
EP: 11.Other Investigational Treatment Options for SMA
EP: 12.Insurance Considerations for SMA Therapies
EP: 13.Optimizing Multidisciplinary Care Approaches for the Future of SMA Management
EP: 14.Final Panel Thoughts on the Management of SMA
Clinical Brief: Disease-Modifying Therapies for Spinal Muscular Atrophy (SMA)
Main Discussion Topics
- Detailed description of splice modifiers (nusinersen and risdiplam) as key treatments for older patients with SMA
- Mechanism and limitations of gene replacement therapy (onasemnogene abeparvovec [Zolgensma])
- Administration considerations for different treatment options
- Potential challenges and adverse events associated with gene therapy
Key Points for Physicians
- Nusinersen requires intrathecal administration via lumbar puncture, with quarterly maintenance dosing.
- Risdiplam is an oral daily medication now available in tablet form, improving adherence.
- Gene therapy (onasemnogene abeparvovec) delivers a functional copy of SMN1 but is currently limited to patients younger than 2 years in the US.
- Gene therapy carries risks including hepatic inflammation, cardiac events, and thrombocytopenia, requiring intensive monitoring.
Notable Insights
Patient preferences regarding treatment administration (daily oral medication vs quarterly intrathecal injection) may influence therapy selection, with some older patients preferring the less frequent dosing schedule of nusinersen despite its more invasive administration.
Clinical Significance
Selection of disease-modifying therapy for older patients with SMA currently involves choosing between nusinersen and risdiplam based on administration considerations, access to medical facilities, and patient preference, while gene therapy research continues for older populations.
Integrated Care for Chronic Conditions: A Randomized Care Management Trial
December 3rd 2025The authors sought to understand the differential impact of payer-led community-based care management approaches on stakeholder-oriented outcomes for publicly insured adults with multiple chronic conditions.
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Managed Care Reflections: A Q&A With A. Mark Fendrick, MD, and Michael E. Chernew, PhD
December 2nd 2025To mark the 30th anniversary of The American Journal of Managed Care (AJMC), each issue in 2025 includes a special feature: reflections from a thought leader on what has changed—and what has not—over the past 3 decades and what’s next for managed care. The December issue features a conversation with AJMC Co–Editors in Chief A. Mark Fendrick, MD, director of the Center for Value-Based Insurance Design and a professor at the University of Michigan in Ann Arbor; and Michael E. Chernew, PhD, the Leonard D. Schaeffer Professor of Health Care Policy and the director of the Healthcare Markets and Regulation Lab at Harvard Medical School in Boston, Massachusetts.
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