Slide 1: Interim Results From the Ongoing RESPOND Study
Interim Results From the Ongoing RESPOND Study Evaluating Nusinersen in Children With Spinal Muscular Atrophy Previously Treated With Onasemnogene Abeparvovec Proud C,1 Parsons JA,2 Kuntz NL,3 Brandsema JF,4 Finkel RS,5 Swoboda KJ,6 Masson R,7 Foster R,8 Liu Y,9 Makepeace C,8 Singhi S,9 Youn B,9 Par
Slide 2: Disclosures
Disclosures • CP: advisory boards and consultant for AveXis, Biogen, and Sarepta; speaker for AveXis and Biogen; Principal Investigator of clinical studies for Astellas, AveXis, Biogen, Catabasis, CSL Behring, Pfizer, PTC, Sarepta, and Scholar Rock • JAP: advisor and consultant for AveXis, Biogen, a
Slide 3: Acknowledgements
Acknowledgements The authors thank the children who are participating in this study and their parents/guardians and family members, without whom this effort cannot succeed The authors also thank the people who are contributing to this study, including the study site principal investigators, clinical
Slide 4: RESPOND study design
RESPOND study design • RESPOND is a Phase 4, multicenter, single-arm, open-label study evaluating nusinersen in participants with SMA who have previously received OA and have suboptimal clinical status as determined by the Investigator • Analysis objective: Provide baseline characteristics and inter
Slide 5: RESPOND key eligibility criteria
RESPOND key eligibility criteria AE = adverse event; IV = intravenous; OA = onasemnogene abeparvovec; SMA = spinal muscular atrophy; SMN2 = survival motor neuron 2 aAdditional criterion: alanine transaminase or aspartate transaminase ≤ 2 × upper limit of normal at Screening and within 7 days before
Slide 6: RESPOND key eligibility criteria and analysis groups
RESPOND key eligibility criteria and analysis groups Key RESPOND analysis groups Age ≤ 9 mo at First Nusinersen Dose Age > 9 mo at First Nusinersen Dose • Age ≤ 9 mo at first nusinersen dosed • Age > 9 mo up to ≤ 36 mo at first nusinersen dose • 2 SMN2 copies • ≥ 1 SMN2 copiese AE = adverse event; I
Slide 7: Interim analyses
Interim analyses Cutoff date for the interim analysis: 15 November 2022 Interim Set (n = 29) Safety Set (n = 38) • Children who received ≥ 1 dose of nusinersen who had the • All children who received ≥ 1 dose of nusinersen as of the opportunity to complete the Day 183 assessment as of the data cut d
Slide 8: Baseline demographics and SMA history (Interim Set)
Baseline demographics and SMA history (Interim Set) Age at First Nusinersen Dose ≤ 9 mo Age at First Nusinersen Dose > 9 mo 2 SMN2 Copies 2 SMN2 Copies 3 SMN2 Copies Demographics and SMA History n = 14 n = 12 n=3 Male / female, n (%) 9 (64.3) / 5 (35.7) 7 (58.3) / 5 (41.7) 3 (100) / 0 Age at SMA sym
Slide 9: Baseline disease characteristics (Interim Set)
Baseline disease characteristics (Interim Set) • The majority of participants had low CMAP ulnar amplitude (≤ 1 mV) at Baseline Age at First Nusinersen Dose ≤ 9 mo Age at First Nusinersen Dose > 9 mo 2 SMN2 Copies 2 SMN2 Copies 3 SMN2 Copies Disease Characteristics n = 14 n = 12 n=3 Achieved motor m
Slide 10: Most participants had Investigator-reported suboptimal clinical status in multiple domains at Baseline
Most participants had Investigator-reported suboptimal clinical status in multiple domains at Baseline Participants With Suboptimal Age at First Nusinersen Age at First Nusinersen Dose > 9 mo Clinical Status in Each Domain Dose ≤ 9 mo at Baseline 2 SMN2 Copies (n = 14) 2 SMN2 Copies (n = 12) 3 SMN2
Slide 11: Most participants with Investigator-reported suboptimal motor function at Baseline improved at Day 183
Most participants with Investigator-reported suboptimal motor function at Baseline improved at Day 183 • The majority with suboptimal swallowing/feeding ability or respiratory function at Baseline had no changes; some improved Participants With Suboptimal Age at First Nusinersen Age at First Nusiner
Slide 12: Most participants had Caregiver-reported suboptimal clinical status in multiple domains at Baseline
Most participants had Caregiver-reported suboptimal clinical status in multiple domains at Baseline Participants With Suboptimal Age at First Nusinersen Age at First Nusinersen Dose > 9 mo Clinical Status in Each Domain Dose ≤ 9 mo; at Baseline 2 SMN2 Copies (n = 14) 2 SMN2 Copies (n = 12) 3 SMN2 Co
Slide 13: Most participants with Caregiver-reported suboptimal motor function at Baseline improved at Day 183
Most participants with Caregiver-reported suboptimal motor function at Baseline improved at Day 183 • Many with suboptimal swallowing/feeding ability at Baseline improved • The majority with suboptimal respiratory function at Baseline had no changes Participants With Suboptimal Age at First Nusiners
Slide 14: Total HINE-2 Score
4 Mean total HINE-2 scores increased from Baseline to Day 183 Total HINE-2 Scores by Age at Visit Maximum 26 score 24 22 20 18 Total HINE-2 Score 16 Actual Mean (SD) Mean (SD) HINE-2 Scores Change 14 Age at First from 12 Nusinersen Baseline to Dose n Baseline n Day 183 n Day 183 10 8 ≤ 9 mo, 2 14 3.
Slide 15: Total CHOP INTEND Score
5 Mean total CHOP INTEND scores increased from Baseline to Day 183 in younger group and remained stable in older group Total CHOP INTEND Scores by Age at Visit Maximum 64 score 60 56 52 Total CHOP INTEND Score 48 44 40 Actual Mean (SD) Mean (SD) 36 CHOP INTEND Scores Change Age at First from 32 Nusi
Slide 16: Total CHOP INTEND Score
6 Mean total CHOP INTEND scores increased from Baseline to Day 183 among those unable to sit without support at Screening Total CHOP INTEND Scores by Age at Visit Among Those Unable to Sit Without Support at Screening Maximum 64 score 60 56 52 Actual Mean (SD) Mean (SD) CHOP INTEND Scores Change Tot
Slide 17: Adverse events reported after a median of ~230 days on study (Safety Set)
Adverse events reported after a median of ~230 days on study (Safety Set) Overall Population Proportion of Participants With Any AEs Overall Population Safety Parameters, n (%) N = 38 and Severity, n (%) N = 38 Participants dosed 38 (100) No AEs 7 (18.4) Time on study, median (range), d 230.5 (28.0–
Slide 18: Summary & Conclusions
Summary & Conclusions At Day 183: • Most participants with suboptimal motor function at Baseline improved • Many with Caregiver-reported suboptimal swallowing/feeding ability at Baseline improved; Investigators most frequently reported no change in this domain • Many with suboptimal respiratory func