Spinal Muscular Atrophy (SMA) is a progressive neurodegenerative disorder caused by a deletion/mutation of the SMN1 gene. Nusinersen and onasemnogene abeparvovec-xioi (zolgensma) are FDA approved therapies.
We describe the use of dual therapies in a group of patients treated under AveXis Inc.’s managed access program.
Data from 28 infants at 18 sites were obtained by surveys completed by treating physicians. Outcomes analyzed were treatment timelines, delivery strategies, motor milestones achieved, and adverse events.
The median age at survey was 9 (IQR= 8-12) months. Median age at zolgensma treatment was 7 (IQR= 4.4-9) months. Time from zolgensma treatment to data collection was 3.1 (IQR= 3-4.6) months. 57% of treated babies achieved head control, 43% rolled, and 32% were able to sit independently. These milestones were met 2 months later than WHO guidelines for unaffected babies. 14.3% of enrolled patients meet CDC/WHO age appropriate standards for head control, 17.9% meet these standards for rolling and 21.5% meet age appropriate standards for sitting. Adverse events were reported in 93%. Most common AEs included fever (64% n=18), respiratory events (43% n=12), and elevated transaminases (36% n=10) with 36% requiring hospitalization. Zolgensma administration occurred at a median of 34.5 (IQR= 8.5-84) days post nusinersen dose. 50% of zolgensma infusions were done in an inpatient unit with an observation period of 16 (IQR= 4.5-23.5) hours.
Dual therapy in babies with SMA was well tolerated. Additional studies to determine if outcomes are improved in those treated with both nusinersen and zolgensma compared to mono therapy would help inform clinical decision making.