Background: Spinal muscular atrophy type 1 (SMA1) is the leading genetic cause of infant mortality for which therapies, including AVXS-101 (onasemnogene abeparvovec, Zolgensma ® ) gene replacement therapy, are emerging. Objective: This study evaluated the effectiveness of AVXS-101 in infants with spinal muscular atrophy type 1 (SMA1) compared with a prospective natural history cohort and a cohort of healthy infants. Methods: Twelve SMA1 infants received the proposed therapeutic dose of AVXS-101 (NCT02122952). Where possible, the following outcomes were compared with a natural history cohort of SMA1 infants (n = 16) and healthy infants (n = 27) enrolled in the NeuroNEXT (NN101) study (NCT01736553): event-free survival, CHOP-INTEND scores, motor milestone achievements, compound muscle action potential (CMAP), and adverse events. Results: Baseline characteristics of SMA1 infants in the AVXS-101 and NN101 studies were similar in age and genetic profile. The proportion of AVXS-101-treated infants who survived by 24 months of follow-up was higher compared with the NN101 study (100% vs 38%, respectively). The average baseline CHOP-INTEND score for NN101 SMA1 infants was 20.3, worsening to 5.3 by age 24 months; the average baseline score in AVXS-101-treated infants was 28.2, improving to 56.5 by age 24 months. Infants receiving AVXS-101 achieved motor milestones, such as sitting unassisted and walking. Improvements in CMAP peak area were observed in AVXS-101-treated infants at 6 and 24 months (means of 1.1 and 3.2 mV/s, respectively).

Background: This study characterizes motor function responses after early dosing of AVXS-101 (onasemnogene abeparvovec) in gene replacement therapy in infants with severe spinal muscular atrophy type 1 (SMA1). Methods: This study is a follow-up analysis of 12 infants with SMA1 who received the proposed therapeutic dose of AVXS-101 in a Phase 1 open-label study (NCT02122952). Infants were grouped according to age at dosing and baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores: (1) early dosing/low motor, dosed age less than three months with scores <20 (n ¼ 3), (2) late dosing, dosed at age three months or greater (n ¼ 6), and (3) early dosing/high motor, dosed age less than three months with scores 20 (n ¼ 3). Results: Early dosing/low motor group demonstrated a mean gain of 35.0 points from a mean baseline of 15.7, whereas the late dosing group had a mean gain of 23.3 from a mean baseline of 26.5. The early dosing/high motor group quickly reached a mean score of 60.3, near the scale maximum (64), from a mean baseline of 44.0. Despite a lower baseline motor score, the early dosing/low motor group achieved sitting unassisted earlier than the late dosing group (mean age: 17.0 vs 22.0 months). The early dosing/high motor group reached this milestone earliest (mean age: 9.4 months). Conclusions: The rapid, significant motor improvements among infants with severe SMA1 treated with AVXS-101 at an early age highlight the importance of newborn screening and early treatment and demonstrate the therapeutic potential of AVXS-101 regardless of baseline motor function.

Spinal muscular atrophy is a progressive, recessively inherited monogenic neurologic disease, the genetic root cause of which is the absence of a functional survival motor neuron 1 gene. Onasemnogene abeparvovec (formerly AVXS-101) is an adeno-associated virus serotype 9 vector-based gene therapy that delivers a fully functional copy of the human survival motor neuron gene. We report anti–adeno-associated virus serotype 9 antibody titers for patients with spinal muscular atrophy when they were screened for eligibility in the onasemnogene abeparvovec clinical trials (intravenous and intrathecal administration) and managed access programs (intravenous). Through December 31, 2019, 196 patients and 155 biologic mothers were screened for anti–adeno-associated virus serotype 9 binding antibodies with an enzyme-linked immunosorbent assay. Of these, 15 patients (7.7%) and 23 biologic mothers (14.8%) had titers >1:50 on their initial screening tests. Eleven patients (5.6%) had elevated titers on their final screening tests. The low percentage of patients with exclusionary antibody titers indicates that most infants with spinal muscular atrophy type 1 should be able to receive onasemnogene abeparvovec. Retesting may identify patients whose antibody titers later decrease to below the threshold for treatment, and retesting should be considered for patients with anti–adeno-associated virus serotype 9 antibody titers >1:50.

The average total charges for a single SMA1 admission were higher than those of the no CCC group. Because most infants with SMA1 require multiple hospitalizations per year, previous estimates may dramatically underestimate the direct costs associated with HRU. Further studies are required to determine the indirect costs and societal impacts of SMA1.

Study design: Prospective, unblinded, multicenter, randomized, controlled, cross-over study assessing user preference and ease of use characteristics of two gel intermittent catheters in 81 self-catheterizing wheelchair-using men. Objectives: To evaluate the male user's preference between a 30-cm and a 40-cm intermittent catheter (Apogee Intermittent Catheter, Hollister Incorporated, Libertyville, IL, USA) regarding the ease of insertion and removal, ability to control the catheter during insertion, bladder emptying confidence and ease of draining urine into a receptacle or connecting to a urine bag. Setting: Multiple institutions in the United States. Methods: Subjects were randomized to order of catheter use, using both 10 test catheters (30-cm) and 10 control catheters (40 cm). All catheters were 12 or 14 French and identical in design and composition, except length. Safety was assessed during the entire study period regarding adverse events (AE) and adverse device events (ADE). Subjects evaluated their ease of use characteristics after each catheter use and final catheter preference. Results: Subjects preferred the Apogee 40-cm intermittent catheter (91.4%) over the 30-cm length (8.6%). The preference was due to subject confidence of complete bladder emptying (70%), more satisfactory length (74%) and easier to drain into a receptacle (58%) with a portable urinal being the most utilized (37%), followed by toilet (35%). The only AE/ADE reported was minor urethral bleeding in one subject and minor pain in another subject, both with the 30-cm catheter. None were reported with the 40-cm catheter. Conclusions: The Apogee 40-cm catheter was the preferred intermittent catheter due to subject confidence in bladder emptying, ease of catheter manipulation and the ease of draining urine into a receptacle.