Longer-term Safety Profile of Nusinersen in Infantile- and Later-Onset SMA: Interim Results From the ENDEAR-SHINE and CHERISH-SHINE Studies


Gene targeted therapies

Poster Number: 82


Basil Darras, MD, Michelle A. Farrar, Eugenio Mercuri, MD, Richard Finkel, MD, Richard Foster, Ishir Bhan, Daniela Ramirez-Schrempp, Janice Wong, MD, MS, Wildon Farwell, MD, MPH


1. Boston Children's Hospital, 2. Sydney Children’s Hospital and UNSW Sydney, 3. Department of Paediatric Neurology,Catholic University, Rome , 4. Nemours Children’s Hospital, University of Central Florida College of Medicine, 5. Biogen, 6. Biogen, 7. Biogen, 8. Biogen, 9. Biogen

Background: Clinical trials have demonstrated a favorable benefit:risk profile for nusinersen and established clinically meaningful efficacy on motor function.
Objectives: To report the safety profile of nusinersen in the SHINE study (NCT02594124) for participants first treated with nusinersen in ENDEAR or CHERISH.
Approach: SHINE is an ongoing, 5-year, open-label extension study for participants who previously participated in nusinersen clinical trials. All participants are receiving 12mg nusinersen every 4 months (SHINE protocol amended from every 6 month dosing for CHERISH).
Results: Among nusinersen-treated participants, 65/80 in ENDEAR and 83/84 in CHERISH transitioned to SHINE. As of 15 October 2018, nusinersen-treated ENDEAR-SHINE participants had been on study for a median (range) of 997.5 (6–1517) days and CHERISH-SHINE for 1175.0 (461–1422) days. In SHINE, 64/65 (98%) of ENDEAR-SHINE and 73/83 (88%) of CHERISH-SHINE participants reported ≥1 AE. The most common AEs in participants continuing nusinersen treatment were pyrexia (66%), upper respiratory tract infection (URTI, 38%), pneumonia (31%), nasopharyngitis (29%), vomiting (23%), ear infection (26%), decreased oxygen saturation (23%), and scoliosis (20%) for ENDEAR-SHINE, and pyrexia (35%), URTI (27%), cough (25%), vomiting (22%) and nasopharyngitis (24%) for CHERISH-SHINE. In SHINE, AEs possibly related to lumbar puncture reported ≤72 hours from dosing occurred in 3 (5%) ENDEAR-SHINE and 17 (20%) CHERISH-SHINE participants. AEs associated with other antisense oligonucleotides, including thrombocytopenia (2%, 0%) and proteinuria (0%, 6%), were low for ENDEAR- and CHERISH-SHINE, respectively. Median ALT, AST, and bilirubin levels remained stable during SHINE. There were no cases meeting Hy’s Law criteria, no AE reports of liver failure and no cases of hydrocephalus.
Conclusions: Safety findings after longer-term nusinersen treatment (up to ~4 years) in SHINE were consistent with those previously reported.
Study Support: Biogen