Newborn screening (NBS) for spinal muscular atrophy (SMA) in the United States (US): Early Findings from the RESTORE registry


Clinical Trials

Poster Number: 65


Laurent Servais MD, PhD, Darryl C De Vivo MD, Janbernd Kirschner , Eugenio Mercuri MD, PhD, Francesco Muntoni MD, Eduardo F Tizzano , Susana Quijano Roy , Kayoko Saito , Melissa Menier , Nicole LaMarca , Frederick A Anderson , Omar Dabbous , Richard Finkel MD


1. MDUK Oxford Neuromuscular Centre, 2. Departments of Neurology and Pediatrics, Columbia University Irving Medical Center, New York, NY, US, 3. Clinic for Neuropediatrics and Muscle Disease, University Medical Center Freiburg, Freiburg, Germany, 4. Universita Cattolica del Sacro Cuore, 5. Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK, 6. Department of Clinical and Molecular Genetics, Hospital Valle Hebron, Barcelona, Spain, 7. Garches Neuromuscular Reference Center, APHP Raymond Poincare University Hospital, Garches, France, 8. Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan, 9. Novartis Gene Therapies, Bannockburn, IL, US, 10. Novartis Gene Therapies, Bannockburn, IL, US, 11. Center for Outcomes Research, Department of Surgery, UMMS, Worcester, MA, US, 12. Novartis Gene Therapies, Bannockburn, IL, US, 13. Translational Neuroscience Program, St. Jude Children's Research Hospital, Memphis, TN, US

Disease-modifying treatments for SMA have dramatically improved prognoses for children afflicted with this debilitating neurodegenerative condition. Timely intervention is critical for preservation of motor function and, in children with SMA type 1, for survival and independence from ventilatory support. While NBS for SMA may facilitate early treatment, which is generally associated with more favorable outcomes, quantitative real-world data are lacking.

The RESTORE registry is an ongoing, prospective, multicenter, multinational, observational study of SMA patients. We stratified patients with two SMN2 copies or a clinical diagnosis of SMA type 1 into two groups based on method of diagnosis: NBS/prenatal screening or clinical diagnosis. We compared age at diagnosis, age at first treatment, and time from diagnosis to treatment between the groups using Wilcoxon rank sum test. Analyses were performed with SAS Version 9.4 (Cary, NC).

As of 04Aug2020, 60 patients met analysis criteria (15 NBS/prenatal diagnosis; 45 clinically diagnosed). All patients were enrolled and treated in the US. For NBS/prenatally identified patients vs. clinically diagnosed patients, mean (SD) age at diagnosis, age at first treatment, and time from diagnosis to treatment, respectively, were 0.7 (1.39) vs. 3.5 (2.69) months, a mean difference of 2.8 (2.69) months (P<0.0001); 1.7 (1.50) vs. 4.2 (3.08) months, a mean difference of 2.6 (2.78) months (P<0.0001); and 0.9 (0.70) vs. 0.7 (0.84) months; a difference of -0.2 (0.81) months (P=0.2165 NS). Updated data including outcomes will be presented.

Our analysis provides real-world evidence that NBS for SMA is associated with significantly earlier diagnosis and intervention. Time from diagnosis to first treatment was not significantly different between patients identified by NBS/prenatal screening vs. those diagnosed clinically. Our study may also stimulate discussion and suggest new lines of inquiry regarding barriers to NBS implementation and reasons for delay between diagnosis and treatment.