Prof. John F. Brandsema (Philadelphia, PA / US), Dr. René Ramseger (München / DE), Julie A. Parsons (Aurora, CO / US), Nancy L. Kuntz (Chicago, IL / US), Crystal Proud (Norfolk, VA / US), Dr Richard S. Finkel (Memphis, TN / US), Kathryn J. Swoboda (Boston, MA / US), Riccardo Masson (Mailand / IT), Yingying Liu (Cambridge, MA / US), Corinne Makepeace (Maidenhead / GB), Angela Paradis (Cambridge, MA / US), Zdenek Berger (Cambridge, MA / US), Kathleen Somera-Molina (Cambridge, MA / US)
Abstract-Text (inkl. Referenzen)
Introduction: We report baseline (BL) characteristics and interim safety from RESPOND (NCT04488133), a study of nusinersen in children with SMA treated with OA ≥2 mo previously.
Methods: Participants have ≥1 SMN2 copy, are age ≤36 mo, nusinersen-naïve, and have suboptimal clinical status (investigator-determined) at BL in ≥1 of 4 domains: motor function, respiratory support, swallowing/feeding ability, and other. Participants receive 12-mg nusinersen in 4 loading doses followed by maintenance doses every 4 mo. Recruitment is ongoing.
Results: As of 15 August 2022, 34 children were dosed. Median time from OA treatment to first nusinersen dose was 6.9 (range: 3–31) mo. At BL, 28/34 children had suboptimal clinical status in ≥2 domains after OA; motor function (n=33) and respiratory function (n=22) were most common. BL mean±SD HINE-2: 6.7±5.7 (n=33). Median duration on nusinersen: 183 (range: 1–540) days. AEs were typical of SMA; most common were upper respiratory tract infection (n=6) and viral upper respiratory tract infection (n=5). 2 participants had mild proteinuria considered nusinersen-related, which resolved. 9 had serious AEs: all considered unrelated to nusinersen and resolved. No deaths or post-lumbar puncture syndrome occurred. Additional data will be presented.
Conclusions: In RESPOND, most enrolled children previously treated with OA had suboptimal clinical status in ≥2 domains. Interim safety was overall consistent with nusinersen"s safety profile.