Trial Outcomes & Findings for Pre-Symptomatic Study of Intravenous Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2 (NCT NCT03505099)

Last Updated: 2026-01-26

Results Overview

Defined by the Bayley Scales of Infant and Toddler Development (BSID) Gross Motor (GM) subtest performance criteria number 26, confirmed by video recording, as a participant who sits for at least 30 seconds without assistance from another person or object. The participant was allowed to use their upper extremities.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

30 participants

Primary outcome timeframe

From Day 1 up to 18 months of age visit

Results posted on

2026-01-26

Participant Flow

A total of 30 participants took part in the trial at 16 sites in the United States, the United Kingdom, Belgium, Canada, Australia and Japan between April 2018 and June 2021.

A total of 44 participants were screened, of which 14 were screen failures and 30 were enrolled and received study drug. One participant had 4 copies of SMN2. This participant was excluded from all analysis populations and data is not reported due to privacy concerns.

Participant milestones

Participant milestones
Measure	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2 Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10\^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2 Participants with bi-allelic deletions of SMN1 and 3 copies of SMN2 received a single dose of AVXS-101 administered as an IV infusion over 60 minutes at a dose of 1.1 × 10\^14 vg/kg on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Overall Study STARTED	14	15
Overall Study Received AVXS-101	14	15
Overall Study COMPLETED	14	15
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pre-Symptomatic Study of Intravenous Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2 n=14 Participants Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10\^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2 n=15 Participants Participants with bi-allelic deletions of SMN1 and 3 copies of SMN2 received a single dose of AVXS-101 administered as an IV infusion over 60 minutes at a dose of 1.1 × 10\^14 vg/kg on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued	Total n=29 Participants Total of all reporting groups
Age, Categorical <=18 years	14 Participants n=25 Participants	15 Participants n=25 Participants	29 Participants n=50 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=25 Participants	0 Participants n=25 Participants	0 Participants n=50 Participants
Age, Categorical >=65 years	0 Participants n=25 Participants	0 Participants n=25 Participants	0 Participants n=50 Participants
Sex: Female, Male Female	10 Participants n=25 Participants	9 Participants n=25 Participants	19 Participants n=50 Participants
Sex: Female, Male Male	4 Participants n=25 Participants	6 Participants n=25 Participants	10 Participants n=50 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=25 Participants	2 Participants n=25 Participants	6 Participants n=50 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=25 Participants	13 Participants n=25 Participants	23 Participants n=50 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=25 Participants	0 Participants n=25 Participants	0 Participants n=50 Participants
Race/Ethnicity, Customized Asian	2 Participants n=25 Participants	2 Participants n=25 Participants	4 Participants n=50 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=25 Participants	1 Participants n=25 Participants	1 Participants n=50 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=25 Participants	0 Participants n=25 Participants	1 Participants n=50 Participants
Race/Ethnicity, Customized White	7 Participants n=25 Participants	10 Participants n=25 Participants	17 Participants n=50 Participants
Race/Ethnicity, Customized Other	4 Participants n=25 Participants	2 Participants n=25 Participants	6 Participants n=50 Participants
SMN2 gene modifier mutation (c.859G>C) Present	0 Participants n=25 Participants	0 Participants n=25 Participants	0 Participants n=50 Participants

PRIMARY outcome

Timeframe: From Day 1 up to 18 months of age visit

Population: Intent-to-Treat (ITT) population (cohort 1) - All enrolled participants with bi-allelic SMN1 deletions and 2 copies of SMN2 without the SMN2 gene modifier mutation (c.859G\>C) who received AVXS-101.

Outcome measures

Outcome measures
Measure	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2 n=14 Participants Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10\^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Cohort 1: Number of Participants Who Achieved Sitting Alone for at Least 30 Seconds	14 Participants

PRIMARY outcome

Timeframe: From Day 1 up to 24 months of age visit

Population: ITT population (cohort 2) - All enrolled participants with bi-allelic SMN1 deletions and 3 copies of SMN2 without the SMN2 gene modifier mutation (c.859G\>C) who received AVXS-101.

Defined by the BSID GM subtest performance criteria number 40, confirmed by video recording, as a participant who stands alone for at least 3 seconds unsupported.

Outcome measures

Outcome measures
Measure	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2 n=15 Participants Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10\^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Cohort 2: Number of Participants Who Achieved Standing Alone for at Least 3 Seconds	15 Participants

SECONDARY outcome

Timeframe: From Day 1 up to 14 months of age

Population: ITT population (cohort 1) - All enrolled participants with bi-allelic SMN1 deletions and 2 copies of SMN2 without the SMN2 gene modifier mutation (c.859G\>C) who received AVXS-101.

Event-free survival at 14 months of age was defined as the number of participants who did not die, did not require permanent ventilation and did not withdraw from the study by 14 months of age.

Outcome measures

Outcome measures
Measure	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2 n=14 Participants Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10\^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Cohort 1: Event-free Survival at 14 Months of Age	14 Participants

SECONDARY outcome

Timeframe: From Day 1 up to 18 months of age

Population: ITT population (cohort 1) - All enrolled participants with bi-allelic SMN1 deletions and 2 copies of SMN2 without the SMN2 gene modifier mutation (c.859G\>C) who received AVXS-101.

The ability to maintain weight at or above the third percentile without the need for non-oral or mechanical feeding support was defined by meeting the following criteria at each visit up to 18 months of age: * Did not receive nutrition through mechanical support (i.e., feeding tube) * Maintained weight (≥ third percentile for age and sex as defined by World Health Organization \[WHO\] guidelines) consistent with the participant's age at the assessment.

Outcome measures

Outcome measures
Measure	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2 n=14 Participants Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10\^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Cohort 1: Number of Participants Who Achieved the Ability to Maintain Weight at or Above the Third Percentile Without the Need for Non-Oral or Mechanical Feeding Support	13 Participants

SECONDARY outcome

Timeframe: From Day 1 up to 24 months of age visit

Population: ITT population (cohort 2) - All enrolled participants with bi-allelic SMN1 deletions and 3 copies of SMN2 without the SMN2 gene modifier mutation (c.859G\>C) who received AVXS-101.

Defined by the BSID GM subtest performance criteria number 43, confirmed by video recording, as a participant who takes 5 coordinated independent steps.

Outcome measures

Outcome measures
Measure	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2 n=15 Participants Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10\^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Cohort 2: Number of Participants Who Achieved the Ability to Walk Alone	14 Participants

Adverse Events

Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2

Serious events: 5 serious events

Other events: 14 other events

Deaths: 0 deaths

Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2 n=14 participants at risk Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10\^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2 n=15 participants at risk Participants with bi-allelic deletions of SMN1 and 3 copies of SMN2 received a single dose of AVXS-101 administered as an IV infusion over 60 minutes at a dose of 1.1 × 10\^14 vg/kg on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Ear and labyrinth disorders Middle ear effusion	7.1% 1/14 • Number of events 1 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).	0.00% 0/15 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).
Gastrointestinal disorders Inguinal hernia	7.1% 1/14 • Number of events 1 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).	0.00% 0/15 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).
Infections and infestations Croup infectious	7.1% 1/14 • Number of events 1 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).	0.00% 0/15 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).
Infections and infestations Pyelonephritis	7.1% 1/14 • Number of events 1 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).	0.00% 0/15 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).
Metabolism and nutrition disorders Hypercalcaemia	7.1% 1/14 • Number of events 1 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).	0.00% 0/15 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	7.1% 1/14 • Number of events 1 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).	0.00% 0/15 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).
Infections and infestations Ear infection	0.00% 0/14 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).	6.7% 1/15 • Number of events 1 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).
Infections and infestations Pharyngitis	0.00% 0/14 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).	6.7% 1/15 • Number of events 1 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).
Nervous system disorders Lethargy	0.00% 0/14 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).	6.7% 1/15 • Number of events 1 • Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).

Other adverse events

Additional Information

EMEA Medical Information

Novartis Gene Therapies EU Limited

Phone: +353 (1) 566-2364

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Depending on local requirements, Sponsor's consent necessary before publication of study, or Sponsor can review results communications before public release with a right to request changes to communications regarding trial results between 40 to 60 and up to 90 or 120 days, as applicable, from the time submitted to Sponsor for review to remove references to Sponsor's Confidential Information or delay results communications to permit Sponsor to obtain appropriate Intellectual Property protection.
Publication restrictions are in place

Restriction type: OTHER