Safety Profile of Nusinersen in Presymptomatic and Infantile-Onset Spinal Muscular Atrophy (SMA): Interim Results From the NURTURE and ENDEAR-SHINE Studies
Basil T. Darras1, Darryl C. De Vivo2, Michelle A. Farrar3, Eugenio Mercuri4, Richard S. Finkel5, Richard Foster6, Wildon Farwell6, Ishir Bhan6
1Boston Children’s Hospital, 2Columbia University Irving Medical Center, 3Sydney Children’s Hospital and UNSW Sydney, 4Catholic University, 5Nemours Children’s Hospital, 6Biogen

To report the safety profile of nusinersen using interim data from the ongoing NURTURE (NCT02386553) and ENDEAR-SHINE (NCT02594124) studies.

Several clinical trials have demonstrated a favorable benefit:risk profile for nusinersen.
NURTURE participants were ≤6 weeks at first dose, clinically presymptomatic, and genetically diagnosed with SMA. ENDEAR participants were ≤7 months at screening and had symptomatic infantile-onset SMA, and following completion of ENDEAR were eligible to transition to the SHINE open-label extension study. Nusinersen 12 mg was administered every 4 months.
At the 29 March 2019 data cut, the median (range) time on study in NURTURE was 33.9 (25.3–45.1) months. The adverse events (AEs) with the greatest incidence in NURTURE were: pyrexia, 21/25 (84%); upper respiratory tract infection, 19/25 (76%); cough, 13/25 (52%); nasopharyngitis, 13/25 (52%); and vomiting, 10/25 (40%). As of 15 October 2018, nusinersen-treated ENDEAR-SHINE participants had been on study (ENDEAR and SHINE) for a median (range) of 997.5 (6–1517) days. The most common AEs during SHINE in participants continuing nusinersen treatment from ENDEAR were: pyrexia, 43/65 (66%); upper respiratory tract infection, 25/65 (38%); pneumonia, 20/65 (31%); nasopharyngitis, 19/65 (29%); and ear infection, 17/65 (26%). There were no clinically relevant trends relating to thrombocytopenia or proteinuria in either study cohort, nor any cases meeting Hy’s Law criteria. There were no cases of hydrocephalus in either population.

After up to ~3.75 years of treatment in NURTURE and ~4 years in SHINE, safety findings were consistent with those reported previously. AEs associated with other antisense oligonucleotides (thrombocytopenia and proteinuria) were low in NURTURE and ENDEAR-SHINE, with no clinically relevant trends, and there were no safety concerns relating to liver function.

Study Supported by: Biogen