Risdiplam in Symptomatic SMA, Nusinersen Preserves Swallowing, Ataluren Delays Ambulation in DMD

This week Neurology News Network covered part 1 of the FIREFISH study evaluating risdiplam in symptomatic type 1 spinal muscular atrophy, the phase 2 open-label NURTURE study of nusinersen, and the effects of ataluren in patients with nonsense mutation Duchenne muscular dystrophy.

Welcome to this special edition of Neurology News Network. I’m Marco Meglio. Please excuse our appearance this week as a majority of the US workforce, including the NeurologyLive team, moves to working remote as we come together to help reduce the spread of the novel coronavirus. This week’s episode is centered around the recent MDA Clinical and Scientific Conference.

New data from part 1 of the FIREFISH study (NCT02913482) of risdiplam (Evrysdi; PTC Therapeutics) in infants with symptomatic type 1 spinal muscular atrophy (SMA) show that in the 0.2 mg/kg daily high-dose cohort B, 88% of infants were event-free after 24 months. Additionally, 59% of those infants were able to sit without support for at least 5 seconds, as measured by the Gross Motor Scale of Bayley Scales of Infant & Toddler Development Edition 3 (BSID-III) scores at 24 months, an improvement from 41% at 12 months. All 7 of the infants achieving that milestone at 12 months maintained it by 24 months. Of 14 infants with the data available at month 24, 93% of infants were alive and able to feed orally. As well, 100% maintained the ability to swallow, of which 86% were able to feed exclusively orally.

Results from the ongoing phase 2 open-label NURTURE study evaluating nusinersen in infants who initiated treatment prior to the onset of clinical spinal muscular atrophy demonstrated preserved swallowing over a long-term period.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 who had a median age at last visit of 3.8 years, 92% of participants maintained the ability to swallow. Swallowing function was assessed using the Parent Assessment of Swallowing Ability 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.

Data from a recent study suggest that ataluren delays loss of ambulation in patients with nonsense mutation Duchenne muscular dystrophy. In Study 019 patients received ataluren for a mean of 988 days (2.7 years) before loss of ambulation (LoA). These patients had a median age of 15.5 years at loss of ambulation, compared to 13.3 years in those receiving standard of care (SoC). Ataluren with SoC was associated with a delay in loss of ambulation of around 2.2 years compared to SoC alone. The researchers wrote that “approximately 10% [to] 15% of patients have a nonsense mutation (nm) in the DMD gene, resulting in the generation of a premature stop codon, which prevents translation of a full-length, functional dystrophin protein. Ataluren promotes readthrough of the in-frame premature stop codon, enabling production of full-length dystrophin.”

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