Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial

Kevin A. Strauss; Michelle A. Farrar; Francesco Muntoni; Kayoko Saito; Jerry R. Mendell; Laurent Servais; Hugh J. McMillan; Richard S. Finkel; Kathryn J. Swoboda; Jennifer M. Kwon; Craig M. Zaidman; Claudia A. Chiriboga; Susan T. Iannaccone; Jena M. Krueger; Julie A. Parsons; Perry B. Shieh; Sarah Kavanagh; Sitra Tauscher-Wisniewski; Bryan E. McGill; Thomas A. Macek

doi:10.1038/s41591-022-01866-4

Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial

Kevin A. Strauss, Michelle A. Farrar, Francesco Muntoni, Kayoko Saito, Jerry R. Mendell, Laurent Servais, Hugh J. McMillan, Richard S. Finkel, Kathryn J. Swoboda, Jennifer M. Kwon, Craig M. Zaidman, Claudia A. Chiriboga, Susan T. Iannaccone, Jena M. Krueger, Julie A. Parsons, Perry B. Shieh, Sarah Kavanagh, Sitra Tauscher-Wisniewski, Bryan E. McGill, Thomas A. Macek

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Abstract

Abstract: SPR1NT (NCT03505099) was a Phase III, multicenter, single-arm study to investigate the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated at ≤6 weeks of life. Here, we report final results for 14 children with two copies of SMN2, expected to develop spinal muscular atrophy (SMA) type 1. Efficacy was compared with a matched Pediatric Neuromuscular Clinical Research natural-history cohort (n = 23). All 14 enrolled infants sat independently for ≥30 seconds at any visit ≤18 months (Bayley-III item #26; P < 0.001; 11 within the normal developmental window). All survived without permanent ventilation at 14 months as per protocol; 13 maintained body weight (≥3rd WHO percentile) through 18 months. No child used nutritional or respiratory support. No serious adverse events were considered related to treatment by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for children expected to develop SMA type 1, highlighting the urgency for universal newborn screening.

Original language	English
Pages (from-to)	1381-1389
Number of pages	9
Journal	Nature medicine
Volume	28
Issue number	7
DOIs	https://doi.org/10.1038/s41591-022-01866-4
State	Published - Jul 2022

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Strauss, K. A., Farrar, M. A., Muntoni, F., Saito, K., Mendell, J. R., Servais, L., McMillan, H. J., Finkel, R. S., Swoboda, K. J., Kwon, J. M., Zaidman, C. M., Chiriboga, C. A., Iannaccone, S. T., Krueger, J. M., Parsons, J. A., Shieh, P. B., Kavanagh, S., Tauscher-Wisniewski, S., McGill, B. E., & Macek, T. A. (2022). Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial. Nature medicine, 28(7), 1381-1389. https://doi.org/10.1038/s41591-022-01866-4

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title = "Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial",

abstract = "Abstract: SPR1NT (NCT03505099) was a Phase III, multicenter, single-arm study to investigate the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated at ≤6 weeks of life. Here, we report final results for 14 children with two copies of SMN2, expected to develop spinal muscular atrophy (SMA) type 1. Efficacy was compared with a matched Pediatric Neuromuscular Clinical Research natural-history cohort (n = 23). All 14 enrolled infants sat independently for ≥30 seconds at any visit ≤18 months (Bayley-III item #26; P < 0.001; 11 within the normal developmental window). All survived without permanent ventilation at 14 months as per protocol; 13 maintained body weight (≥3rd WHO percentile) through 18 months. No child used nutritional or respiratory support. No serious adverse events were considered related to treatment by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for children expected to develop SMA type 1, highlighting the urgency for universal newborn screening.",

author = "Strauss, {Kevin A.} and Farrar, {Michelle A.} and Francesco Muntoni and Kayoko Saito and Mendell, {Jerry R.} and Laurent Servais and McMillan, {Hugh J.} and Finkel, {Richard S.} and Swoboda, {Kathryn J.} and Kwon, {Jennifer M.} and Zaidman, {Craig M.} and Chiriboga, {Claudia A.} and Iannaccone, {Susan T.} and Krueger, {Jena M.} and Parsons, {Julie A.} and Shieh, {Perry B.} and Sarah Kavanagh and Sitra Tauscher-Wisniewski and McGill, {Bryan E.} and Macek, {Thomas A.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = jul,

doi = "10.1038/s41591-022-01866-4",

language = "English",

volume = "28",

pages = "1381--1389",

journal = "Nature medicine",

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Strauss, KA, Farrar, MA, Muntoni, F, Saito, K, Mendell, JR, Servais, L, McMillan, HJ, Finkel, RS, Swoboda, KJ, Kwon, JM, Zaidman, CM, Chiriboga, CA, Iannaccone, ST, Krueger, JM, Parsons, JA, Shieh, PB, Kavanagh, S, Tauscher-Wisniewski, S, McGill, BE & Macek, TA 2022, 'Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial', Nature medicine, vol. 28, no. 7, pp. 1381-1389. https://doi.org/10.1038/s41591-022-01866-4

TY - JOUR

T1 - Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1

T2 - the Phase III SPR1NT trial

AU - Strauss, Kevin A.

AU - Farrar, Michelle A.

AU - Muntoni, Francesco

AU - Saito, Kayoko

AU - Mendell, Jerry R.

AU - Servais, Laurent

AU - McMillan, Hugh J.

AU - Finkel, Richard S.

AU - Swoboda, Kathryn J.

AU - Kwon, Jennifer M.

AU - Zaidman, Craig M.

AU - Chiriboga, Claudia A.

AU - Iannaccone, Susan T.

AU - Krueger, Jena M.

AU - Parsons, Julie A.

AU - Shieh, Perry B.

AU - Kavanagh, Sarah

AU - Tauscher-Wisniewski, Sitra

AU - McGill, Bryan E.

AU - Macek, Thomas A.

PY - 2022/7

Y1 - 2022/7

N2 - Abstract: SPR1NT (NCT03505099) was a Phase III, multicenter, single-arm study to investigate the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated at ≤6 weeks of life. Here, we report final results for 14 children with two copies of SMN2, expected to develop spinal muscular atrophy (SMA) type 1. Efficacy was compared with a matched Pediatric Neuromuscular Clinical Research natural-history cohort (n = 23). All 14 enrolled infants sat independently for ≥30 seconds at any visit ≤18 months (Bayley-III item #26; P < 0.001; 11 within the normal developmental window). All survived without permanent ventilation at 14 months as per protocol; 13 maintained body weight (≥3rd WHO percentile) through 18 months. No child used nutritional or respiratory support. No serious adverse events were considered related to treatment by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for children expected to develop SMA type 1, highlighting the urgency for universal newborn screening.

AB - Abstract: SPR1NT (NCT03505099) was a Phase III, multicenter, single-arm study to investigate the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated at ≤6 weeks of life. Here, we report final results for 14 children with two copies of SMN2, expected to develop spinal muscular atrophy (SMA) type 1. Efficacy was compared with a matched Pediatric Neuromuscular Clinical Research natural-history cohort (n = 23). All 14 enrolled infants sat independently for ≥30 seconds at any visit ≤18 months (Bayley-III item #26; P < 0.001; 11 within the normal developmental window). All survived without permanent ventilation at 14 months as per protocol; 13 maintained body weight (≥3rd WHO percentile) through 18 months. No child used nutritional or respiratory support. No serious adverse events were considered related to treatment by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for children expected to develop SMA type 1, highlighting the urgency for universal newborn screening.

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U2 - 10.1038/s41591-022-01866-4

DO - 10.1038/s41591-022-01866-4

M3 - Article

C2 - 35715566

AN - SCOPUS:85132253340

SN - 1078-8956

VL - 28

SP - 1381

EP - 1389

JO - Nature medicine

JF - Nature medicine

IS - 7

ER -

Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial

Abstract

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