Baseline Characteristics/Initial Safety Results in RESPOND: A Phase 4 Study of Nusinersen in Children with SMA Who Received Onasemnogene Abeparvovec


Clinical Trials

Poster Number: 85


Julie Parsons, MD, Children's Hospital Colorado, Aurora, CO, 80045 USA, Riccardo Masson, MD, Fondazione IRCCS Istituto Neurologico Carlo Besta, Crystal Proud, MD, Children's Hospital of The King's Daughters, John Brandsema, MD, The Children's Hospital of Philadelphia, Richard S Finkel, MD, Center for Experimental Neurotherapeutics, St. Jude Children’s Research Hospital, Memphis, TN, US, Kathryn J Swoboda, MD, Massachusetts General Hospital, Boston, MA, USA, Erika Finanger, MD, Oregon Health and Science University, Yingying Liu, PhD, Biogen, Cambridge, MA, USA, Corinne Makepeace, MBBS, Biogen, Maidenhead, UK, Angela D. Paradis, ScD, Biogen, Cambridge, MA, USA, Zdenek Berger, PhD, Biogen, Cambridge, MA, USA, Joanne Wagner, PhD, MS, Biogen, Kathleen Somera-Molina, PhD, MSci, Biogen, Cambridge, MA, USA

Background: Onasemnogene abeparvovec is an adeno-associated viral (AAV) vector gene therapy for SMA in children age <2 years. Preclinical animal models and limited human postmortem studies have demonstrated incomplete transduction of motor neurons by the AAV9 vector. Nusinersen has the potential to increase SMN protein in untransduced motor neurons, thereby, potentially bringing additional clinical benefit to patients with SMA. In RESPOND, children ?36 months old who have ?1 SMN2 copy, are nusinersen-naïve, and have suboptimal clinical status following onasemnogene abeparvovec administered ?3 months previously, receive the approved 12 mg nusinersen regimen of 4 loading doses followed by maintenance doses every 4 months. Suboptimal clinical status (investigator-determined) includes ?1 of the following domains: motor function, respiratory support, swallowing/feeding ability, and other. Study recruitment is ongoing.
Objectives: To provide baseline characteristics of participants and initial safety findings in RESPOND (NCT04488133), an ongoing, single-arm study evaluating nusinersen treatment in children with SMA previously treated with onasemnogene abeparvovec.
Results: As of 16 August 2021, 9 children (median [range] age 16.4 [5–30] months) were enrolled; 1 discontinued (parent/guardian decision). Most (8/9) had 2 SMN2 copies. Baseline mean ± SD Hammersmith Infant Neurological Examination (HINE)-2 total score was 8.1 ± 5.3. At baseline, all participants demonstrated suboptimal clinical status in ?2 domains; motor and respiratory function were most common. Median duration on nusinersen and safety follow-up period was 64 days (range: 1–183 days). Most common adverse events (AEs) were infections (4 participants, 7 events [ear infection, viral gastroenteritis, parainfluenza virus infection, pneumonia, upper respiratory tract infection (URTI), viral URTI]) and vomiting (2 participants). Two participants had serious AEs, which were unrelated to nusinersen: parainfluenza virus infection (2 events in 1 participant) and URTI. No deaths or post-lumbar puncture syndrome events occurred. Additional results will be presented.
Conclusions: Baseline characteristics of children in RESPOND showed suboptimal clinical status in multiple domains including motor and respiratory functions despite onasemnogene abeparvovec treatment. Initial safety findings indicate no AEs or serious AEs were considered related to nusinersen.
Study Support: Biogen