FEASIBILITY OF INDIRECT TREATMENT COMPARISONS FOR OAV101 IT IN SPINAL MUSCULAR ATROPHY
Author(s)
Nicholas Riley1, Almuth Marx2, Orlando Dohring3, IFTekhar KHAN, PhD3, Rabiah Begum, BSc, MSc, PhD3, Emmet Campbell4, Sajjad Rafiq, MSc, PhD3, Grace McCarthy, MSc5, Christopher Drudge, PhD6, Niki Srikanth6, Roya Gavanji7, Paul Spin, PhD8, Pamela Vo, MS, PharmD9;
1Novartis, Basel, Switzerland, 2Novartis Deutschland GmbH, Nuernberg, Germany, 3Novartis, London, United Kingdom, 4Novartis, Ireland, 5Dublin, Ireland, 6EVERSANA, Burlington, ON, Canada, 7Canada, 8EVERSANA, Canada, 9EVERSANA, Basel, Switzerland
1Novartis, Basel, Switzerland, 2Novartis Deutschland GmbH, Nuernberg, Germany, 3Novartis, London, United Kingdom, 4Novartis, Ireland, 5Dublin, Ireland, 6EVERSANA, Burlington, ON, Canada, 7Canada, 8EVERSANA, Canada, 9EVERSANA, Basel, Switzerland
OBJECTIVES: Assess the feasibility of indirect treatment comparisons (ITCs) of intrathecal onasemnogene abeparvovec (OAV101 IT) versus other disease-modifying therapies (DMTs) for spinal muscular atrophy (SMA) to support health technology assessments (HTAs) including the European Union Joint Clinical Assessment (JCA).
METHODS: Relevant clinical trials and observational studies were identified via a systematic literature review. Studies were assessed qualitatively for network connectivity, outcome availability, and alignment with OAV101 IT trials. Cross-study heterogeneity was evaluated based on study design, population, and outcome characteristics. As patient-level data were available for OAV101 IT and intravenous OAV101 (OAV101 IV) trials, ITC feasibility of these DMTs was assessed quantitatively.
RESULTS: Anchored ITCs of OAV101 IT versus nusinersen and risdiplam in a DMT-naïve population aged ≥2 years were deemed feasible using clinical trial data as were unanchored ITCs in a DMT-experienced population aged ≥2 years, for age-appropriate outcomes (e.g., change from baseline in Hammersmith Functional Motor Assessment - Expanded score). Certain populations (e.g., aged 6 months to 2 years) could not be addressed using ITCs due to a lack of comparable study data. Although observational studies including those using SMA registry data were assessed, none were found to be appropriate for an ITC given study limitations and the availability of higher-quality clinical trial data for comparators. An ITC of OAV101 IT and OAV101 IV was deemed infeasible in both DMT-naïve and-experienced populations due to limited sample size and insufficient overlap in the trial populations.
CONCLUSIONS: Based on clinical evidence for SMA DMTs, ITCs were feasible for OAV101 IT versus nusinersen and risdiplam in both DMT-naïve and -experienced populations aged ≥2 years. However, an ITC of OAV101 IT versus OAV101 IV was not feasible. These findings confirm that comprehensive feasibility assessments are necessary for informing evidence generation strategies across often wide-ranging populations and outcomes of interest to JCA and other HTAs.
METHODS: Relevant clinical trials and observational studies were identified via a systematic literature review. Studies were assessed qualitatively for network connectivity, outcome availability, and alignment with OAV101 IT trials. Cross-study heterogeneity was evaluated based on study design, population, and outcome characteristics. As patient-level data were available for OAV101 IT and intravenous OAV101 (OAV101 IV) trials, ITC feasibility of these DMTs was assessed quantitatively.
RESULTS: Anchored ITCs of OAV101 IT versus nusinersen and risdiplam in a DMT-naïve population aged ≥2 years were deemed feasible using clinical trial data as were unanchored ITCs in a DMT-experienced population aged ≥2 years, for age-appropriate outcomes (e.g., change from baseline in Hammersmith Functional Motor Assessment - Expanded score). Certain populations (e.g., aged 6 months to 2 years) could not be addressed using ITCs due to a lack of comparable study data. Although observational studies including those using SMA registry data were assessed, none were found to be appropriate for an ITC given study limitations and the availability of higher-quality clinical trial data for comparators. An ITC of OAV101 IT and OAV101 IV was deemed infeasible in both DMT-naïve and-experienced populations due to limited sample size and insufficient overlap in the trial populations.
CONCLUSIONS: Based on clinical evidence for SMA DMTs, ITCs were feasible for OAV101 IT versus nusinersen and risdiplam in both DMT-naïve and -experienced populations aged ≥2 years. However, an ITC of OAV101 IT versus OAV101 IV was not feasible. These findings confirm that comprehensive feasibility assessments are necessary for informing evidence generation strategies across often wide-ranging populations and outcomes of interest to JCA and other HTAs.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
SA26
Topic
Study Approaches
Topic Subcategory
Meta-Analysis & Indirect Comparisons
Disease
SDC: Musculoskeletal Disorders (Arthritis, Bone Disorders, Osteoporosis, Other Musculoskeletal), SDC: Rare & Orphan Diseases