Cure SMA Conference 2023 - NBS in Multiple Databases

Transcript

1. • Spinal muscular atrophy (SMA) is a neurodegenerative disease due to a mutation in or deletion of the SMN1 gene, and early intervention is essential to preserve motor function.1 • SMA was added to the United States (U.S.) federal Recommended Uniform Screening Panel (RUSP) in July 2018, but implementation and timing of screening occurs at the state level. • Forty-eight states and Washington D.C. have implemented newborn screening (NBS) programs for SMA as of May 2023, representing 99% of all U.S. births.2 Figure 1: States screening and not screening for SMA in the U.S. • Cure SMA, a patient advocacy organization that provides patient/family support and funding for SMA research and care, manages multiple databases which include individuals identified by SMA NBS in the U.S. • The objective of this analysis was to describe SMA characteristics and outcomes from each data source, side-by-side, to give a more holistic picture of SMA NBS in the U.S. Newborn Screening for Spinal Muscular Atrophy in the United States: Perspectives from Multiple Real World Data Sources Sarah Whitmire MS, Lisa Belter MPH, Alesa Monk MBA, Jackie Glascock PhD, Jessica Clark, Erica Jorgensen, Mary Curry ND, Mary Schroth MD, FAAP, FCCP Cure SMA, Elk Grove Village, IL • In total, 282, 68, 87, and 427 individuals met inclusion criteria in the MD, NBSR, CDR, and aggregated SPHL, respectively. [Table 1] • Across data sources, most individuals had 2 copies of SMN2 (47-51%). [Figure 2] Figure 2: SMN2 copy number distribution, by data source • Median age at SMN1 test was 7 days in MD (n=183), 7 days in NBSR (n=63), and 10 days in CDR (n=79) [combined range: 0-373]. [Figure 3] • Mean ages at SMN1 test ranged from 8.4 days (NBSR) to 23 days (CDR). Figure 3: Mean and median ages at first recorded/reported SMN1 test, by data source • Median age at first SMA treatment was 27.5 days in both the MD (n=134) and NBSR (n=48) and 29 days in the CDR (n=77) [combined range: 0-396]. [Figure 4] • Mean ages at first SMA treatment ranged from 41.3 days (NBSR) to 49.6 days (MD). • Age at first SMA treatment was lower for individuals with 2 copies of SMN2, and medians ranged from 21 days (CDR) to 24 days (MD/NBSR). Figure 4: Age at first SMA treatment, by data source • In the NBSR: Median reported ages at milestone achievements were within published normal ranges for development; however, there was variability. [Figure 5] • In the CDR: Clinicians reported that 65% of individuals with 2 copies of SMN2 and 100% of individuals with 3+ copies of SMN2 that were at least 24 months old at the time of eCRF completion could walk assisted or unassisted. [Figure 6] • This cross-sectional analysis used data from four Cure SMA databases: • Membership database (MD): one of the largest patient/parent reported SMA data repositories, with over 9,500 individuals with SMA. • NBS Registry (NBSR): a parent/caregiver-reported database collected through an online survey with over 65 individuals identified via NBS. • Clinical Data Registry (CDR): an IRB-governed database comprised of electronic medical record-sourced data from the Cure SMA Care Center Network (CCN) and is linked to clinician-entered electronic case report forms. Over 800 affected individuals participate in the CDR. • State public health labs (SPHL): limited aggregated data collected from over 40 state labs on over 7.8 million individuals. • Inclusion criteria included U.S. residence, identification by NBS, and birthdate after 7/1/2018. • All available data from birth through 1/23/2023 were used in this analysis. • This was a descriptive analysis, and no adjustments or statistical analyses were performed. Table 1: Attrition and final cohort sizes • Thank you to the SMA community and the NBS SPHLs for sharing their data. • Thank you to the Cure SMA Care Center Network (CCN) for their commitment to improving care for people with SMA and contributing consented patient data; additionally, thank you to the Cure SMA CCN Registry Committee for providing guidance on CDR processes, quality, and research. Funding for the SMA Care Center Network was provided in part by the Erin Trainor Memorial Fund and the Tyler William Orr Memorial Fund. Since 2018, Cure SMA has partnered with hospitals across the U.S. with the goal to improve healthcare for people with SMA. Every Care Center Network site submits consented patient information and data to the Cure SMA Clinical Data Registry. This data is then analyzed to drive healthcare improvements. • Funding for this research was also provided by the Cure SMA Real World Evidence Collaboration and the Cure SMA Industry Collaboration. The Cure SMA Real World Evidence Collaboration was established in 2021 to leverage the experience, expertise and resources of pharmaceutical and biotechnology companies and nonprofit organizations involved in development of SMA therapeutics to guide the future direction of real world evidence collection and use in SMA. Current members include Biogen, Genentech/Roche, and Novartis Gene Therapies. The Cure SMA Industry Collaboration (SMA-IC) was established in 2016 to leverage the experience, expertise, and resources of pharmaceutical and biotechnology companies, as well as other nonprofit organizations involved in the development of spinal muscular atrophy (SMA) therapeutics to more effectively address a range of scientific, clinical, and regulatory challenges. Current members include Cure SMA, Biogen, Scholar Rock, Novartis Gene Therapies, Biohaven Pharmaceuticals, Epirium Bio, Genentech/Roche, and SMA Europe. Funding for this research was provided by members of the 2018 to 2023 SMA-IC; members included Cure SMA, Astellas Pharmaceuticals, Biogen, Biohaven Pharmaceuticals, Cytokinetics Inc., Epirium Bio, Genentech/Roche, Novartis Gene Therapies, Novartis Pharmaceuticals, Scholar Rock, and SMA Europe. • This analysis further characterizes the incident population with SMA identified by NBS from data collected from multiple sources and perspectives. • Our data show that roughly half the incident population has 2 copies of SMN2. The median ages at SMN1 test were less than 2 weeks, and the median ages at first SMA treatment were less than 1 month. • Overall mean and median ages at first SMA treatment were lower for individuals with 2 copies of SMN2, and there was wider variability for individuals with 4+ copies of SMN2. • The descriptive milestone achievement data emphasizes the impact of early diagnosis and intervention for individuals with SMA. • However, additional analyses to further understand delay in diagnosis and treatment are needed. Methods Background Results Conclusion Acknowledgements MD NBSR CDR SPHL All individuals with SMA 9,968 (100%) 70 (100%) 816 (100%) 480 (100%) eCRF available - - 801 (98.2%) - U.S. resident 7,825 (78.5%) 70 (100%) 766 (95.6%) 480 (100%) Identified by NBS 290 (3.7%) 70 (100%) 90 (11.7%) 480 (100%) Born on or after 7/1/2018 282 (3.6%) 68 (97.1%) 87 (11.4%) 427 (89%) Final cohort 282 68 87 427* 2% 47% 34% 18% 6% 47% 30% 17% 1% 51% 36% 12% 3% 50% 33% 15% 1 copy SMN2 2 copies SMN2 3 copies SMN2 4+ copies SMN2 Membership NBSR CDR State Public Health NBS Labs Mean: 14.1 days Mean: 8.4 days Mean: 23 days Median: 7 days Median: 7 days Median: 10 days 0 5 10 15 20 25 MD (n=183) NBSR (n=63) CDR (n=79) Range: 0-373 Range: 1-25 Range: 0-372 52% 87% 83% 65% 100% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 2 copies SMN2 3 copies SMN2 4+ copies SMN2 Age ≥ 14 months at time of eCRF Age ≥ 24 months at time of eCRF 0 2 4 6 8 10 12 14 16 Hold head (n=47) Roll over (n=35) Sit supported (n=32) Sit unsupported (n=26) Walk (n=6) Reported Age in Months range: 1-7 mo. range: 1-11 mo. range: 1-8 mo. range: 5-10 mo. range: 10-18 mo. Distribution of SMN2 Copy Number Legend: 1-2 copies SMN2 3+ copies SMN2 Unknown PARENT/CAREGIVER REPORTED CLINICIAN REPORTED Figure 5: Reported median age at milestone achievement, in months (NBSR) Figure 6: Achievement of assisted or unassisted walking (CDR) Note: U.S. resident was used as the denominator for attrition steps below the gray line. * May be an overestimate. At least 6 states reported the number of tests instead of individuals. mean x median Note: Age at SMN1 test must be greater than or equal to 0. No data is available for SPHL. Note: Restricted to individuals where all treatment records had known dates, and age at treatment must be greater than or equal to 0 days. No data is available for SPHL. Note: n=35 who reported the age at which the individual achieved either “rolling from back to stomach” or “rolling from stomach to back”. The minimum of both reported ages was used. Note: eCRF completion is based on information in the medical chart at time of submission and may be outdated. Most recent functional status had a “SELECT ONE” response. Two individuals with “stand independently” as the current functional status were not included in this analysis due to uncertainty of whether they were also able to walk assisted. Results Age at First SMA Treatment in Days Age at SMN1 Test in Days References: 1. Verhaart IEC, et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy – a literature review. Orphanet J Rare Dis. 2017;12:124. 2. Cure SMA. Newborn Screening for SMA. https://www.curesma.org/newborn-screening-for-sma/