Preserved swallowing function in infants who initiated nusinersen treatment in the presymptomatic stage of SMA: results from the NURTURE study

Topic:

Clinical Trials

Poster Number: 71

Author(s):

Kathryn J. Swoboda MD, Valeria A. Sansone MD, Darryl C De Vivo MD, Enrico Bertini MD, Wuh-Liang Hwu MD, PhD, Corinne Makepeace , Justin Bohn , Russell Chin , Stephanie Raynaud , Angela D. Paradis ScD

Institutions:

1. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA, 2. Neurorehabilitation Unit, University of Milan, NEMO Clinical Center in Milan, Italy, 3. Departments of Neurology and Pediatrics, Columbia University Irving Medical Center, New York, NY, US, 4. Post-Graduate Bambino Gesù Children’s Research Hospital, Rome, Italy, 5. National Taiwan University Hospital, Taipei, Taiwan, 6. Biogen, Maidenhead, UK, 7. Biogen, Maidenhead, Berkshire, UK, 8. Biogen, Cambridge, MA, USA, 9. Biogen, Cambridge, MA, USA, 10. Biogen, Cambridge, MA, USA

Background: Patients with spinal muscular atrophy (SMA) Types I or II experience deterioration of swallowing function and high levels of bulbar comorbidities such as risk of aspiration pneumonia, choking, and failure to thrive. Without treatment, tube feeding is often needed. Nusinersen has shown significant and clinically meaningful efficacy on motor function and survival endpoints across a broad spectrum of SMA subtypes, with limited data reported to date on bulbar function.
Objectives: To assess swallowing function in NURTURE study participants.
Methods: NURTURE (NCT02386553) is an ongoing, Phase 2, open-label study evaluating nusinersen in infants who initiated treatment prior to the onset of clinical SMA symptoms. Twenty-five participants (n=15 with 2 SMN2 copies, n=10 with 3 SMN2 copies) aged ≤6 weeks at first dose were enrolled and were treated with intrathecal nusinersen 12 mg. Swallowing function was assessed using the Parent Assessment of Swallowing Ability (PASA) questionnaire. The PASA includes 33 questions relating to general feeding, liquid swallowing, solid swallowing, and swallowing concerns over the previous 7 days, and was administered at multiple timepoints after treatment initiation.
Results: As of the February 19, 2020 interim data cut, participants had a median age at last visit of 3.8 (range, 2.8-4.8) years. At the last available assessment (Day 778), 84% were not tube fed (11/15 with 2 SMN2 copies, all with 3 SMN2 copies); of the 4 tube fed participants, 2 participant’s parents answered “always” and 2 answered “often” to being tube fed in the previous 7 days. Ninety-one percent of participants never gagged or choked on liquid food, 87% never gagged or choked on solid food. Eighty-eight percent (21/24) and 96% (23/24) of parents disagreed/strongly disagreed with being concerned over their child choking and aspirating on their food while eating, respectively.
Conclusion: Swallowing ability was maintained in 13/15 participants with 2 SMN2 copies and in 10/10 participants with 3 SMN2 copies who initiated nusinersen treatment. Only 2 participants with 2 SMN2 copies required full-time tube feeding, in contrast to the expectation of nearly universal bulbar insufficiency in this population. Swallowing function continues to be monitored in NURTURE to better understand the efficacy of nusinersen.
Study Support: Biogen