STELLAR Phase 3 Studies to Evaluate the Efficacy and Safety of Salanersen in Infants with Spinal Muscular Atrophy (SMA)

Topic:

Clinical Trials

Poster Number: 199 M

Author(s):

Thomas Crawford, MD, Johns Hopkins University School of Medicine, Crystal Proud, MD, Children’s Hospital of the King’s Daughters, Norfolk, VA, USA, Richard Finkel, MD, St Jude Children's Research Hospital, Eugenio Mercuri, MD, PhD, Paediatric Neurology, Catholic University, Rome, Italy, Centro Clinico Nemo, IRCCS, Rome, Italy, Laurent Servais, MD PhD, University of Oxford, Michelle Farrar, MD, UNSW Sydney, Stephanie Fradette, PharmD, Biogen, Peng Sun, PhD, Biogen, Julia Heo, Pharm.D., Biogen, Sara Alexanian, Biogen, Cambridge, MA, USA, Jennifer Inra, Biogen, Cambridge, MA, USA, Carrie Rubel, PhD, Biogen, Julie Czerkowicz, Biogen, Cambridge, MA, USA, Alissa Verone-Boyle, Biogen, Cambridge, MA, USA, Shirley Wu, Biogen, Cambridge, MA, USA, Yingying Liu, PhD, Biogen, Cambridge, MA, USA, Richard Foster, PhD, Biogen, Leeann Burton, MD, Biogen

Salanersen (BIIB115) is an investigational, intrathecally administered antisense oligonucleotide being developed for the treatment of spinal muscular atrophy (SMA). Salanersen shares a similar mechanism with nusinersen but is designed with novel backbone chemistry to achieve higher potency relative to nusinersen, thus enabling the potential to maximize clinical outcomes with once yearly dosing.
Two linked Phase 3 studies will assess the efficacy and safety of salanersen in infants with SMA who initiate treatment while presymptomatic. STELLAR-1 is an open-label, single-arm study evaluating salanersen in treatment-naive, presymptomatic infants (aged ≤6 weeks) with SMA and 2 or 3 survival motor neuron 2 (SMN2) copies. Participants will receive salanersen 80 mg annually during the 5-year study. Primary endpoints are attainment of World Health Organization motor milestones unexpected without treatment: sitting unsupported at 12-month follow-up and walking independently at 18-month follow-up for participants with 2 and 3 SMN2 copies, respectively. STELLAR-2 is a randomized, double-blind, sham-controlled study evaluating salanersen in infants with SMA and 2 SMN2 copies who received treatment with onasemnogene abeparvovec (OA) at ≤6 weeks of age. Participants are randomized 6 months post-OA to active treatment (salanersen 80 mg annually) or sham control. After the 12-month controlled period, participants in the sham arm will transition to active treatment. Key efficacy endpoints include plasma neurofilament light chain, motor function scales, and electrophysiology between groups at 12-month and 5-year follow-up. Data generated across STELLAR-1 and STELLAR-2 will provide insights on outcomes among infants who receive presymptomatic treatment with salanersen monotherapy, OA monotherapy, and OA followed by salanersen.