EVIDENCE BASE FOR JOINT CLINICAL ASSESSMENT: A CLINICAL SYSTEMATIC LITERATURE REVIEW OF OAV101 IT AND COMPARATORS FOR SPINAL MUSCULAR ATROPHY
Author(s)
Nicholas Riley, BEc, GradDip Clin Epi & Biostat1, Grace McCarthy, MSc2, Sarah Kane3, Jose Esguerra4, Sara A. Kulinski3, Pamela Vo, MS, PharmD5, Christopher Drudge3;
1Novartis, Basel, Switzerland, 2Dublin, Ireland, 3Burlington, ON, Canada, 4Burlington, Canada, 5EVERSANA, Basel, Switzerland
1Novartis, Basel, Switzerland, 2Dublin, Ireland, 3Burlington, ON, Canada, 4Burlington, Canada, 5EVERSANA, Basel, Switzerland
OBJECTIVES: Spinal muscular atrophy (SMA) is a rare genetic disorder leading to progressive muscle weakness and atrophy. Recent advancements in disease-modifying therapies (DMTs) have significantly improved clinical outcomes. Intrathecal onasemnogene abeparvovec (OAV101 IT) is a single-dose gene replacement therapy that addresses the genetic root cause of SMA. A systematic literature review (SLR) was conducted to inform indirect treatment comparisons (ITCs) to support health technology assessments (HTAs), including the European Union Joint Clinical Assessment (JCA), for OAV101 IT.
METHODS: MEDLINE, Embase, Cochrane Controlled Register of Trials, and Cochrane Database of Systematic Reviews were searched via Ovid for records published from January 2014 to September 2025. Grey literature searches included trial registries and HTA reports. Broad inclusion criteria were applied to capture all relevant DMTs and clinical outcomes anticipated from the 30 Member States. Data extraction followed an evidence hierarchy for each relevant PICO per the JCA scope, prioritizing randomized controlled trials (RCTs). Single-arm trials and prospective observational studies (including patient registry studies) were also considered as ITC data sources. Study quality was assessed per JCA guidelines.
RESULTS: Eight RCTs, 21 single-arm trials, and 324 observational studies evaluating safety/efficacy of SMA DMTs (i.e., continually-administered therapies and one-time gene replacement) were included. No head-to-head RCTs were identified for SMA DMTs including nusinersen, risdiplam, and onasemnogene abeparvovec. Most clinical trials involved SMA DMT-naïve patients while few involved SMA DMT-experienced populations. Various motor function scales were used, with the Hammersmith Functional Motor Scale-Expanded and Revised Upper Limb Module most commonly reported. Observational studies presented limited evidence and had critical risk-of-bias.
CONCLUSIONS: Studies identified in this SLR, combined with the evidence hierarchy applied, comprise a foundational high-quality evidence base. This evidence was used to assess the feasibility of conducting comparative effectiveness analyses amongst comparator SMA DMTs for the JCA of OAV101 IT.
METHODS: MEDLINE, Embase, Cochrane Controlled Register of Trials, and Cochrane Database of Systematic Reviews were searched via Ovid for records published from January 2014 to September 2025. Grey literature searches included trial registries and HTA reports. Broad inclusion criteria were applied to capture all relevant DMTs and clinical outcomes anticipated from the 30 Member States. Data extraction followed an evidence hierarchy for each relevant PICO per the JCA scope, prioritizing randomized controlled trials (RCTs). Single-arm trials and prospective observational studies (including patient registry studies) were also considered as ITC data sources. Study quality was assessed per JCA guidelines.
RESULTS: Eight RCTs, 21 single-arm trials, and 324 observational studies evaluating safety/efficacy of SMA DMTs (i.e., continually-administered therapies and one-time gene replacement) were included. No head-to-head RCTs were identified for SMA DMTs including nusinersen, risdiplam, and onasemnogene abeparvovec. Most clinical trials involved SMA DMT-naïve patients while few involved SMA DMT-experienced populations. Various motor function scales were used, with the Hammersmith Functional Motor Scale-Expanded and Revised Upper Limb Module most commonly reported. Observational studies presented limited evidence and had critical risk-of-bias.
CONCLUSIONS: Studies identified in this SLR, combined with the evidence hierarchy applied, comprise a foundational high-quality evidence base. This evidence was used to assess the feasibility of conducting comparative effectiveness analyses amongst comparator SMA DMTs for the JCA of OAV101 IT.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
SA2
Topic
Study Approaches
Topic Subcategory
Literature Review & Synthesis
Disease
SDC: Musculoskeletal Disorders (Arthritis, Bone Disorders, Osteoporosis, Other Musculoskeletal), SDC: Rare & Orphan Diseases