Components of bulbar function in patients with SMA
SMA experts and Novartis Gene Therapies have published post hoc analyses of data from ZOLGENSMA clinical trials to evaluate bulbar function in patients who were presymptomatic and symptomatic for SMA at the time of ZOLGENSMA infusion. Both analyses were descriptive only, no hypotheses were considered. Categorical variables are described as numbers and percentages.1,2
Post hoc analyses of data from completed clinical trials were conducted. All trials included patients with bi-allelic mutations in the SMN1 gene.1,2
Methods: Descriptive post hoc analyses of ZOLGENSMA clinical trial data1
In these analyses, bulbar function was defined as: Integrity within cranial nerves that enables an individual to (1) meet nutritional needs by mouth without pulmonary instability and (2) demonstrate verbal communication abilities.
Four endpoints from available clinical trial data were selected to represent key components of bulbar function. Together these components formed the composite endpoint of bulbar function. Verbal communication was not assessed in SPR1NT and not included in the composite analysis for presymptomatic patients.
Composite definition and assessment of bulbar function in SMA1
Airway protection
No occurrence of adverse events (such as aspiration or aspiration pneumonia) due to compromised airway protection.
Swallowing
No evidence of swallowing impairment identified by a clinician (via clinical or fluoroscopic markers).
Full oral nutrition
Received 76% to 100% of nutrition orally (per HCP or parent report) and did not require non-oral feeding support.
Verbal communication
Vocalize at least 2 different, distinct vowel sounds (achievement of item 6 or above on the Bayley Scales of Infant and Toddler Development, 3rd Edition Expressive Communication subtest).
Descriptive post hoc analysis of bulbar data from presymptomatic patients treated with ZOLGENSMA (N=29)1
In the post hoc analysis, data for normal swallow, full oral nutrition, and airway protection from the SPR1NT trial were reviewed. Verbal communication was not measured in SPR1NT and was therefore not included in the analysis. Performance at the last evaluated time point was used to judge achievement of individual and composite bulbar function outcomes.
Individual endpoints achieved at end of SPR1NT
bThe need for nutrition support and the percentage of nutrition received via oral intake were assessed via parent report or provider observation at the end of study visit. A lack of non-oral nutrition support (ie, enteral nutrition via feeding tube or parenteral nutrition) and receiving 76–100% of nutrition via oral intake together represented maximum oral nutrition for this analysis.
cA lack of adverse events of aspiration or aspiration pneumonia was considered evidence of the ability to maintain pulmonary stability.
"He’s talking. He doesn’t stop talking. Which is a another kind of major thing. Not everyone with SMA Type 1 is verbal."
— Matt, Donovan’s Dad (Donovan, treated at ~2 months old)
Descriptive post hoc analysis of pooled data from 65 symptomatic patients treated with ZOLGENSMA2
This analysis included pooled data from START, STR1VE-US, and STR1VE-EU.
Data for normal swallow, full oral nutrition, airway protection, and verbal communication were reviewed.a-d
Patients were included in this post hoc analysis if they were <6 months of age at the time of infusion and received the therapeutic dose (or equivalent).
Performance at the last evaluated time point was used to judge achievement of individual and composite bulbar function outcomes.
Individual endpoints for bulbar functione,f
Normal Swallow n (%) | Full oral nutrition n (%) | Airway protection n (%) | Verbal communication n (%) | |
Baseline End of study | 57 (88) 60 (92) | 55 (85) 49 (75) | 65 (100) 60 (92) | 4 (20) 19 (95) |
bThe need for nutrition support and percentage of oral intake was assessed via parent report or provider observation. For this analysis, patients were required to receive 76% to 100% of nutrition via oral intake, in addition to a lack of non-oral nutrition support.
cA lack of adverse events of aspiration or aspiration pneumonia was considered evidence of the ability to maintain pulmonary stability.
dCommunication was only assessed for patients from native English-speaking families in START and STR1VE-US. The communication endpoint for this post-hoc analysis was considered achievement of item #6 or greater on the Bayley Expressive Communication subtest.
ePercentages calculated as a proportion of patients with available data (N=65 for swallow, nutrition, and airway protection; N=20 for communication). End of study represents the last evaluated time point during the study period.
fCommunication was only assessed for patients from native English-speaking families in START and STR1VE-US. At baseline, communication was assessed for 20 patients in STR1VE-US; before end of study, communication was assessed for 4 patients in START and 16 in STR1VE-US.
"He can eat. He can talk. He’s very vocal. He received gene therapy at 27 days old, it really did change his prognosis."
— Nicole, Matteo’s mom (Matteo, treated at ~1 month old)