Swallowing Function Possibly Nonissue With Nusinersen in Presymptomatic SMA

Kathryn Swoboda, MD

Results from the ongoing phase 2 open-label NURTURE study (NCT02386553) evaluating nusinersen (Spinraza; Biogen) in infants who initiated treatment prior to the onset of clinical spinal muscular atrophy (SMA) demonstrated preserved swallowing over a long-term period.¹

The data was presented at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference 2021, March 15-18, by lead investigator Kathryn Swoboda, MD, Katherine B. Sims Endowed Chair in Neurogenetics, and director, Neurogenetics Program, Massachusetts General Hospital. Swoboda and colleagues concluded that “swallowing function continues to be monitored in NURTURE to better understand the efficacy of nusinersen over a longer duration of follow-up.”

Among a cohort of 25 infants with SMA (15 with 2 SMN2 copies, 10 with 3 SMN2 copies) who had a median age at last visit of 3.8 years (range, 2.8-4.8), 92% of participants (n = 23) maintained the ability to swallow. Swallowing function was assessed using the Parent Assessment of Swallowing Ability (PASA) questionnaire, which included 33 questions related to general feeding, drinking liquids, eating solid foods, and parental assessment of swallowing concerns over the previous 7 days.

READ MORE: Ataluren Delays Loss of Ambulation in Patients With Nonsense Mutation DMD

Patients included in the study were consistently rated, on average, as never to rarely experiencing difficulty in terms of general feeding, drinking liquids, and eating solid foods over a 2-year period. Notably, these results were consistent among both groups with 2 and 3 SMN2 copies, though results were somewhat stronger in participants with 3 copies, as those patients more often reported never having these issues.

None of the patients with 3 SMN2 copies needed to be fed by tube, and 4 of 15 participants with 2 SMN2 copies were identified by PASA as having a feeding tube. More specifically, 2 of the 15 reported “always” tube fed while the other 2 “often” tube fed in the previous 7 days prior to their last assessment.

Over the course of the study, 2 of these 4 participants required invasive ventilation and 3 required noninvasive ventilation. No patients required permanent ventilation or tracheostomy.

All 4 participants gained motor milestones and motor function over time despite the use of a feeding tube. Three of them achieved a Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score greater than 60, and all 4 achieved a CHOP INTEND score greater than 45.

Original data from NURTURE published in June 2020 suggested that infants with SMA experienced unprecedented survival rates with treatment of nusinersen, demonstrated by the ability for patients to maintain and achieve gains in motor function for up to 4.8 years. As of February 2020, 100% of the patients treated in the study were alive and free of the need for permanent ventilation.²

The analysis also showed that all study participants who were previously able to walk with assistance (92%) and walk independently (88%) maintained that ability over the 11 months since the last data cut. As well, over 11 months of follow-up, 1 child gained the ability to walk with assistance—pushing the mark to 96%of all study participants—and also reached the maximum score on the CHOP-INTEND scale, thus increasing the total number of study participants who achieved the maximum score to 84% (n = 21).

For more coverage of MDA 2021, click here.

REFERENCES

1. Swoboda KJ, Sansone VA, De Vivo DC, et al. Preserved swallowing function in infants who initiated nusinersen treatment in the presymptomatic stage of SMA: results from the NURTURE study. Presented at MDA Clinical and Scientific Conference 2021; March 15–18.

2. New Results From Landmark NURTURE Study Show That Pre-Symptomatic SMA Patients Treated With SPINRAZA® (nusinersen) Continue to Demonstrate Sustained Benefit From Treatment. Biogen. June 10, 2020. Accessed March 15, 2021. globenewswire.com/news-release/2020/06/10/2046158/0/en/New-Results-From-Landmark-NURTURE-Study-Show-That-Pre-Symptomatic-SMA-Patients-Treated-With-SPINRAZA-nusinersen-Continue-to-Demonstrate-Sustained-Benefit-From-Treatment.html