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Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre‑mRNA splicing modifier that has been widely approved for the treatment of spinal muscular atrophy (SMA). RAINBOWFISH (NCT03779334) is a global, open-label, single-arm, multicentre, Phase 2 study assessing the efficacy, safety and pharmacokinetics/pharmacodynamics of risdiplam in infants with genetically diagnosed and presymptomatic SMA from birth to 6 weeks of age (at first dose), regardless of SMN2 copy number. The study enrolled 26 infants: eight infants had two SMN2 copies, 13 infants had three SMN2 copies and five infants had ≥4 SMN2 copies. The primary efficacy (PE) population (n=5) had two SMN2 copies and baseline compound muscle action potential (CMAP) amplitudes ≥1.5mV. Drug dosage was adjusted to achieve a target exposure of approximately 2,000 ng∙ hr/mL. The primary endpoint was met after 12 months of risdiplam treatment with 4/5 (80%) infants in the PE population able to sit without support for ≥5 seconds (Item 22 of the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development, third edition [BSID-III]). Irrespective of CMAP amplitude, 7/8 infants with two SMN2 copies were able to sit without support for ≥30 seconds (BSID‑III Item 26), including all infants with CMAP amplitude <1.5 mV (n=3). Out of 26 infants, 24 (92%) were able to sit without support, 13 (50%) were able to stand unaided and 12 (46%) were able to walk independently at Month 12, as assessed by the Hammersmith Infant Neurological Examination, Module 2. At Month 12, all infants were alive without permanent ventilation, maintained their swallowing and feeding abilities and no adverse events (AEs) led to withdrawal or treatment discontinuation. Most AEs were not considered treatment-related and resolved over time. One infant met the criteria for development of clinically manifested SMA. Here we report, for the first-time, the 2-year efficacy and safety data from RAINBOWFISH. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral muscular dystrophy (FSHD) is marked by progressive muscle weakness in facial, shoulder girdle, upper arms, lower limbs, and abdominal muscles, causing considerable morbidity and decreasing quality of life. There are currently no approved therapies for FSHD. The primary form, FSHD1, is linked to harmful overactivity of the DUX4 gene, resulting in muscle atrophy and weakness. Studies indicate that abnormal DUX4 expression triggers inflammatory processes in the initial stages of the disease. Patients with FSHD1 had increased inflammatory and reduced anti-inflammatory cytokines levels, indicating chronic inflammation. IL-6 levels strongly correlate with clinical severity in patients, and with functional scores in patients and FSHD-like mouse models. Here we present the study design of ReInForce (NCT06222827), a bicentric, randomized, double-blind, placebo-controlled, Phase 2 study to investigate the safety and efficacy of satralizumab, an IL-6 receptor inhibitor, in adults with FSHD1. Patients (N=40) will receive 120 mg satralizumab or placebo subcutaneously at Weeks 0, 2, 4 and then every 4 weeks until Week 48. The 48 weeks of the Double-Blind period will be followed by a 48-week Open Label period. The study will evaluate efficacy by assessing changes in muscle composition and function, as well as measures of clinical disease progression. Given the pathological relevance of inflammation in FSHD, and the correlation of IL-6 levels with disease severity, satralizumab may reduce muscle and systemic inflammation, thereby reducing fibrofatty degeneration in FSHD. [ABSTRACT FROM AUTHOR]