Trial Outcomes & Findings for Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in Pediatric Patients With Type 2 Spinal Muscular Atrophy (SMA) (NCT NCT05089656)

Last Updated: 2026-01-13

Results Overview

The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

126 participants

Primary outcome timeframe

Baseline, Week 52 (or Week 48)

Results posted on

2026-01-13

Participant Flow

121 total participants were treated with a single dose of OAV101B (either in Period 1 (even if they did not complete Period 1) or Period 2).

Participant milestones

Participant milestones
Measure	OAV101 First, Then Sham Control OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2
Period 1 - First Intervention (52 weeks) STARTED	75	51
Period 1 - First Intervention (52 weeks) Patients completed follow-up period 1	73	50
Period 1 - First Intervention (52 weeks) Patients completed follow-up period 1 but did not enter treatment period 2	6	4
Period 1 - First Intervention (52 weeks) Patient who completed Week 48 but not Week 52	1	0
Period 1 - First Intervention (52 weeks) Primary reason for not entering treatment period 2	6	4
Period 1 - First Intervention (52 weeks) COMPLETED	67	46
Period 1 - First Intervention (52 weeks) NOT COMPLETED	8	5
Period 2 - 2nd Intervention (12 weeks) STARTED	67	46
Period 2 - 2nd Intervention (12 weeks) COMPLETED	67	46
Period 2 - 2nd Intervention (12 weeks) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	OAV101 First, Then Sham Control OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2
Period 1 - First Intervention (52 weeks) Physician Decision	1	0
Period 1 - First Intervention (52 weeks) Guardian decision	1	0
Period 1 - First Intervention (52 weeks) Adverse Event	0	1
Period 1 - First Intervention (52 weeks) Protocol-specified withdrawal criterion met	6	4

Baseline Characteristics

Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in Pediatric Patients With Type 2 Spinal Muscular Atrophy (SMA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OAV101 First, Then Sham Control n=75 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 n=51 Participants A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2	Total n=126 Participants Total of all reporting groups
Age, Continuous	5.71 years STANDARD_DEVIATION 3.575 • n=210 Participants	5.68 years STANDARD_DEVIATION 3.045 • n=19 Participants	5.70 years STANDARD_DEVIATION 3.358 • n=123 Participants
Sex: Female, Male Female	41 Participants n=210 Participants	23 Participants n=19 Participants	64 Participants n=123 Participants
Sex: Female, Male Male	34 Participants n=210 Participants	28 Participants n=19 Participants	62 Participants n=123 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=210 Participants	5 Participants n=19 Participants	7 Participants n=123 Participants
Race (NIH/OMB) Asian	49 Participants n=210 Participants	25 Participants n=19 Participants	74 Participants n=123 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=210 Participants	0 Participants n=19 Participants	0 Participants n=123 Participants
Race (NIH/OMB) Black or African American	5 Participants n=210 Participants	4 Participants n=19 Participants	9 Participants n=123 Participants
Race (NIH/OMB) White	7 Participants n=210 Participants	7 Participants n=19 Participants	14 Participants n=123 Participants
Race (NIH/OMB) More than one race	0 Participants n=210 Participants	0 Participants n=19 Participants	0 Participants n=123 Participants
Race (NIH/OMB) Unknown or Not Reported	12 Participants n=210 Participants	10 Participants n=19 Participants	22 Participants n=123 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52 (or Week 48)

Population: Full Analysis Set - all participants who were treated in treatment period 1 with a valid measurement (including 1 pt who dropped out between Week 48 and week 52; The data collected at Week 48 are included in this table.) (Participants who early terminated before Week 48 are not included).

Outcome measures

Outcome measures
Measure	OAV101 First, Then Sham Control n=74 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 n=50 Participants A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2	Overall OAV101 in Periods 1 and 2 OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg). * For participants randomized to OAV101B in Period 1: All AEs from Period 1 and 2 * For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All AEs from Period 2
Change From Baseline at the End of Period 1 in the Hammersmith Functional Motor Scale Expanded - Total Score - in the ≥ 2 to < 18 Years Age Group	2.39 Scores on a scale Standard Error 0.439	0.51 Scores on a scale Standard Error 0.532	—

SECONDARY outcome

Timeframe: Baseline, Week 52 (or Week 48)

Population: Full Analysis Set - all participants who were treated in treatment period 1 with a valid measurement in the 2 to \<5 years age group. (Participants who early terminated before Week 48 are not included.)

Outcome measures

Outcome measures
Measure	OAV101 First, Then Sham Control n=41 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 n=29 Participants A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2	Overall OAV101 in Periods 1 and 2 OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg). * For participants randomized to OAV101B in Period 1: All AEs from Period 1 and 2 * For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All AEs from Period 2
Change From Baseline in HFMSE Total Score at the End of Follow-up Period 1 in Treated Patients Compared to Sham Controls in the ≥ 2 to < 5 Years Age Group	3.00 Scores on a scale Standard Error 0.569	1.56 Scores on a scale Standard Error 0.683	—

SECONDARY outcome

Timeframe: Baseline, Week 52 (or Week 48)

The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. The scale consists of 19 scorable items: 18 items scored on 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.

Outcome measures

Outcome measures
Measure	OAV101 First, Then Sham Control n=74 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 n=50 Participants A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2	Overall OAV101 in Periods 1 and 2 OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg). * For participants randomized to OAV101B in Period 1: All AEs from Period 1 and 2 * For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All AEs from Period 2
Change From Baseline in Revised Upper Limb Module (RULM) Total Score at the End of Follow-up Period 1 in Treated Patients Compared to Sham Controls in the ≥ 2 to < 18 Years Age Group	2.44 Scores on a scale Standard Error 0.381	0.92 Scores on a scale Standard Error 0.462	—

SECONDARY outcome

Timeframe: Baseline, Week 52 (or Week 48)

The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. The scale consists of 19 scorable items: 18 items scored on a 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.

Outcome measures

Outcome measures
Measure	OAV101 First, Then Sham Control n=41 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 n=29 Participants A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2	Overall OAV101 in Periods 1 and 2 OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg). * For participants randomized to OAV101B in Period 1: All AEs from Period 1 and 2 * For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All AEs from Period 2
Change From Baseline in the RULM Total Score at the End of Follow-up Period 1 in Treated Patients Compared to Sham Controls in the ≥ 2 to < 5 Years Age Group	3.27 Scores on a scale Standard Error 0.535	1.82 Scores on a scale Standard Error 0.642	—

SECONDARY outcome

Timeframe: Baseline, Week 52 (or Week 48) (end of Period 1)

Outcome measures

Outcome measures
Measure	OAV101 First, Then Sham Control n=74 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 n=50 Participants A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2	Overall OAV101 in Periods 1 and 2 OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg). * For participants randomized to OAV101B in Period 1: All AEs from Period 1 and 2 * For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All AEs from Period 2
% of Participants Who Achieved at Least a 3-point Improvement From Baseline in HFMSE Total Score at the End of Follow-up Period 1 in the ≥ 2 to < 18 Years Age Group	39.2 % of participants Interval 28.07 to 50.31	26.0 % of participants Interval 13.84 to 38.16	—

SECONDARY outcome

Timeframe: Baseline, Week 52 (or Week 48)(end of Period 1)

Outcome measures

Outcome measures
Measure	OAV101 First, Then Sham Control n=41 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 n=29 Participants A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2	Overall OAV101 in Periods 1 and 2 OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg). * For participants randomized to OAV101B in Period 1: All AEs from Period 1 and 2 * For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All AEs from Period 2
% of Participants Who Achieved at Least a 3-point Improvement From Baseline in HFMSE Total Score at the End of Follow-up Period 1 for Participants Aged ≥ 2 to < 5 Years	48.8 % of participants Interval 33.48 to 64.08	37.9 % of participants Interval 20.27 to 55.59	—

SECONDARY outcome

Timeframe: Adverse events are reported from the start of treatment period 1 plus 64 weeks, up to a maximum time period of 64 weeks.

Population: Safety analysis set - all treated pts. AEs for Periods 1 and 2 are combined in the overall OAV101 arm because the same active treatment (and same single dose) was administered in either Period1 or 2. Because this is a gene therapy, which permanently impacts the genetics of the study pt, pts randomized to OAV101 in Period 1 are still considered on treatment with OAV101 in Period 2 (after receiving sham control in Period 2). Therefore, AEs for the Sham arm can only be considered from Period 1.

An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. A Treatment Emergent Adverse Event (TEAE) is defined as an event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments. pt = participant pts = participants

Outcome measures

Outcome measures
Measure	OAV101 First, Then Sham Control n=75 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 n=51 Participants A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2	Overall OAV101 in Periods 1 and 2 n=121 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg). * For participants randomized to OAV101B in Period 1: All AEs from Period 1 and 2 * For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All AEs from Period 2
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events Any treatment-emergent adverse event	74 Participants	46 Participants	104 Participants
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events Any treatment-emergent adverse event related to study treatment	27 Participants	5 Participants	36 Participants
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events Any serious treatment-emergent adverse event	21 Participants	17 Participants	34 Participants
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events Any serious treatment-emergent adverse event related to study treatment	8 Participants	1 Participants	12 Participants
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events Any severe treatment-emergent adverse event	8 Participants	9 Participants	12 Participants
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events Any treatment-emergent adverse event leading to study discontinuation	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events Any treatment-emergent adverse event leading to death	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events Any treatment-emergent adverse event of special interest	12 Participants	7 Participants	21 Participants

SECONDARY outcome

Timeframe: Adverse events are reported from the start of treatment period 1 plus 64 weeks, up to a maximum time period of 64 weeks.

Population: Safety analysis set - all treated participants.

An AESI is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows: * Hepatotoxicity * Thrombocytopenia * Cardiac adverse events * Signs and symptoms that may be suggestive of dorsal root ganglia toxicity * Thrombotic microangiopathy * New malignancies Adverse events for Periods 1 and 2 are combined in the overall OAV101 arm because the same active treatment (and same single dose) was administered in either Period1 or Period 2. Because this is a gene therapy, which permanently impacts the genetics of the study participant, participants randomized to OAV101 in Period 1 are still considered on treatment with OAV101 in Period 2 (after receiving sham control in Period 2). Therefore, adverse events for the Sham arm can only be considered from Period 1.

Outcome measures

Outcome measures
Measure	OAV101 First, Then Sham Control n=75 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 n=51 Participants A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2	Overall OAV101 in Periods 1 and 2 n=121 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg). * For participants randomized to OAV101B in Period 1: All AEs from Period 1 and 2 * For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All AEs from Period 2
Number of Participants With Adverse Events of Special Interest (AESI) Hepatotoxicity	7 Participants	5 Participants	10 Participants
Number of Participants With Adverse Events of Special Interest (AESI) Transient thrombocytopenia	4 Participants	2 Participants	9 Participants
Number of Participants With Adverse Events of Special Interest (AESI) Cardiac adverse events	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events of Special Interest (AESI) Signs and symptoms that may be suggestive of dorsal root ganglia toxicity	2 Participants	1 Participants	3 Participants
Number of Participants With Adverse Events of Special Interest (AESI) Thrombotic microangiopathy	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events of Special Interest (AESI) New malignancies	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to 64 weeks

Population: Safety analysis set - all treated participants.

Intracardiac thrombi is defined as the presence of thrombus on post-baseline echocardiograms. Events for Periods 1 and 2 are combined in the overall OAV101 arm because the same active treatment (and same single dose) was administered in either Period1 or Period 2. Because this is a gene therapy, which permanently impacts the genetics of the study participant, participants randomized to OAV101 in Period 1 are still considered on treatment with OAV101 in Period 2 (after receiving sham control in Period 2). Therefore, events for the Sham arm can only be considered from Period 1.

Outcome measures

Outcome measures
Measure	OAV101 First, Then Sham Control n=75 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 n=51 Participants A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2	Overall OAV101 in Periods 1 and 2 n=121 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg). * For participants randomized to OAV101B in Period 1: All AEs from Period 1 and 2 * For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All AEs from Period 2
Number (and Percentage) of Patients With Intracardiac Thrombi	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to 64 weeks

Population: Safety analysis set - all treated participants.

Low cardiac function is defined as left ventricular ejection fraction \<56% or left ventricular fractional shortening \<28% on post-baseline echocardigrams. Events for Periods 1 and 2 are combined in the overall OAV101 arm because the same active treatment (and same single dose) was administered in either Period1 or Period 2. Because this is a gene therapy, which permanently impacts the genetics of the study participant, participants randomized to OAV101 in Period 1 are still considered on treatment with OAV101 in Period 2 (after receiving sham control in Period 2). Therefore, events for the Sham arm can only be considered from Period 1.

Outcome measures

Outcome measures
Measure	OAV101 First, Then Sham Control n=75 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2	Sham Control First, Then OAV101 n=51 Participants A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Period 2	Overall OAV101 in Periods 1 and 2 n=121 Participants OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg). * For participants randomized to OAV101B in Period 1: All AEs from Period 1 and 2 * For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All AEs from Period 2
Number(and Percentage) of Patients With Low Cardiac Function	8 Participants	9 Participants	17 Participants

Adverse Events

OAV101 Period 1

Serious events: 21 serious events

Other events: 63 other events

Deaths: 0 deaths

Sham Control Period 1

Serious events: 17 serious events

Other events: 43 other events

Deaths: 0 deaths

Overall OAV101 in Periods 1 and 2

Serious events: 34 serious events

Other events: 85 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER